Transcription Factor EB: A Promising Therapeutic Target for Ischemic
Stroke

Jie      Shao; Yue      Lang; Manqiu      Ding; Xiang      Yin; Li      Cui
doi:10.2174/1570159X21666230724095558
Abstract

Transcription factor EB (TFEB) is an important endogenous defensive protein that responds to ischemic stimuli. Acute ischemic stroke is a growing concern due to its high morbidity and mortality. Most survivors suffer from disabilities such as numbness or weakness in an arm or leg, facial droop, difficulty speaking or understanding speech, confusion, impaired balance or coordination, or loss of vision. Although TFEB plays a neuroprotective role, its potential effect on ischemic stroke remains unclear. This article describes the basic structure, regulation of transcriptional activity, and biological roles of TFEB relevant to ischemic stroke. Additionally, we explore the effects of TFEB on the various pathological processes underlying ischemic stroke and current therapeutic approaches. The information compiled here may inform clinical and basic studies on TFEB, which may be an effective therapeutic drug target for ischemic stroke.
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Graphical Abstract

[1]
Mendelson, S.J.; Prabhakaran, S. Diagnosis and management of transient ischemic attack and acute ischemic stroke. JAMA,  2021, 325(11), 1088-1098.
 [http://dx.doi.org/10.1001/jama.2020.26867] [PMID: 33724327]

[2]
Feigin, V.L.; Norrving, B.; Mensah, G.A. Global burden of stroke. Circ. Res.,  2017, 120(3), 439-448.
 [http://dx.doi.org/10.1161/CIRCRESAHA.116.308413] [PMID: 28154096]

[3]
Donnan, G.A.; Fisher, M.; Macleod, M.; Davis, S.M. Stroke. Lancet,  2008, 371(9624), 1612-1623.
 [http://dx.doi.org/10.1016/S0140-6736(08)60694-7] [PMID: 18468545]

[4]
Galluzzi, L.; Bravo-San Pedro, J.M.; Levine, B.; Green, D.R.; Kroemer, G. Pharmacological modulation of autophagy: Therapeutic potential and persisting obstacles. Nat. Rev. Drug Discov.,  2017, 16(7), 487-511.
 [http://dx.doi.org/10.1038/nrd.2017.22] [PMID: 28529316]

[5]
Chen, M.Y.; Dai, Y.S.; Liu, S.Y.; Fan, Y.X.; Ding, Z.X.; Li, D. TFEB biology and agonists at a glance. Cells,  2021, 10(2), 333.
 [http://dx.doi.org/10.3390/cells10020333] [PMID: 33562649]

[6]
Napolitano, G.; Ballabio, A. TFEB at a glance. J. Cell Sci.,  2016, 129(13), 2475-2481.
 [PMID: 27252382]

[7]
Sardiello, M.; Palmieri, M.; di Ronza, A.; Medina, D.L.; Valenza, M.; Gennarino, V.A.; Di Malta, C.; Donaudy, F.; Embrione, V.; Polishchuk, R.S.; Banfi, S.; Parenti, G.; Cattaneo, E.; Ballabio, A. A gene network regulating lysosomal biogenesis and function. Science,  2009, 325(5939), 473-477.
 [http://dx.doi.org/10.1126/science.1174447] [PMID: 19556463]

[8]
Medina, D.L.; Fraldi, A.; Bouche, V.; Annunziata, F.; Mansueto, G.; Spampanato, C.; Puri, C.; Pignata, A.; Martina, J.A.; Sardiello, M.; Palmieri, M.; Polishchuk, R.; Puertollano, R.; Ballabio, A. Transcriptional activation of lysosomal exocytosis promotes cellular clearance. Dev. Cell,  2011, 21(3), 421-430.
 [http://dx.doi.org/10.1016/j.devcel.2011.07.016] [PMID: 21889421]

[9]
Settembre, C.; Di Malta, C.; Polito, V.A.; Arencibia, M.G.; Vetrini, F.; Erdin, S.; Erdin, S.U.; Huynh, T.; Medina, D.; Colella, P.; Sardiello, M.; Rubinsztein, D.C.; Ballabio, A. TFEB links autophagy to lysosomal biogenesis. Science,  2011, 332(6036), 1429-1433.
 [http://dx.doi.org/10.1126/science.1204592] [PMID: 21617040]

[10]
Settembre, C.; De Cegli, R.; Mansueto, G.; Saha, P.K.; Vetrini, F.; Visvikis, O.; Huynh, T.; Carissimo, A.; Palmer, D.; Klisch, T.J.; Wollenberg, A.C.; Di Bernardo, D.; Chan, L.; Irazoqui, J.E.; Ballabio, A. TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop (vol 15, pg 647, 2013). Nat. Cell Biol.,  2013, 15(8), 1016-1016.
 [http://dx.doi.org/10.1038/ncb2814]

[11]
Mansueto, G.; Armani, A.; Viscomi, C.; D’Orsi, L.; De Cegli, R.; Polishchuk, E.V.; Lamperti, C.; Di Meo, I.; Romanello, V.; Marchet, S.; Saha, P.K.; Zong, H.; Blaauw, B.; Solagna, F.; Tezze, C.; Grumati, P.; Bonaldo, P.; Pessin, J.E.; Zeviani, M.; Sandri, M.; Ballabio, A. Transcription factor EB controls metabolic flexibility during exercise. Cell Metab.,  2017, 25(1), 182-196.
 [http://dx.doi.org/10.1016/j.cmet.2016.11.003] [PMID: 28011087]

[12]
Fan, Y.; Lu, H.; Liang, W.; Garcia-Barrio, M.T.; Guo, Y.; Zhang, J.; Zhu, T.; Hao, Y.; Zhang, J.; Chen, Y.E. Endothelial TFEB (transcription factor EB) positively regulates postischemic angiogenesis. Circ. Res.,  2018, 122(7), 945-957.
 [http://dx.doi.org/10.1161/CIRCRESAHA.118.312672] [PMID: 29467198]

[13]
Brady, O.A.; Martina, J.A.; Puertollano, R. Emerging roles for TFEB in the immune response and inflammation. Autophagy,  2018, 14(2), 181-189.
 [http://dx.doi.org/10.1080/15548627.2017.1313943] [PMID: 28738171]

[14]
Gu, S.; Tan, J.; Li, Q.; Liu, S.; Ma, J.; Zheng, Y.; Liu, J.; Bi, W.; Sha, P.; Li, X.; Wei, M.; Cao, N.; Yang, H.T. Downregulation of LAPTM4B contributes to the impairment of the autophagic flux via unopposed activation of mTORC1 signaling during myocardial Ischemia/reperfusion injury. Circ. Res.,  2020, 127(7), e148-e165.
 [http://dx.doi.org/10.1161/CIRCRESAHA.119.316388] [PMID: 32693673]

[15]
Li, M.; Wang, Z.; Wang, P.; Li, H.; Yang, L. TFEB: A emerging regulator in lipid homeostasis for atherosclerosis. Front. Physiol.,  2021, 12639920.
 [http://dx.doi.org/10.3389/fphys.2021.639920] [PMID: 33679452]

[16]
Martini-Stoica, H.; Xu, Y.; Ballabio, A.; Zheng, H. The autophagy-lysosomal pathway in neurodegeneration: A TFEB perspective. Trends Neurosci.,  2016, 39(4), 221-234.
 [http://dx.doi.org/10.1016/j.tins.2016.02.002] [PMID: 26968346]

[17]
Bahrami, A.; Bianconi, V.; Pirro, M.; Orafai, H.M.; Sahebkar, A. The role of TFEB in tumor cell autophagy: Diagnostic and therapeutic opportunities. Life Sci.,  2020, 244117341.
 [http://dx.doi.org/10.1016/j.lfs.2020.117341] [PMID: 31972208]

[18]
Zhang, W.; Li, X.; Wang, S.; Chen, Y.; Liu, H. Regulation of TFEB activity and its potential as a therapeutic target against kidney diseases. Cell Death Discov.,  2020, 6(1), 32.
 [http://dx.doi.org/10.1038/s41420-020-0265-4] [PMID: 32377395]

[19]
Cheli, Y.; Ohanna, M.; Ballotti, R.; Bertolotto, C. Fifteen-year quest for microphthalmia-associated transcription factor target genes. Pigment Cell Melanoma Res.,  2010, 23(1), 27-40.
 [http://dx.doi.org/10.1111/j.1755-148X.2009.00653.x] [PMID: 19995375]

[20]
Puertollano, R.; Ferguson, S.M.; Brugarolas, J.; Ballabio, A. The complex relationship between TFEB transcription factor phosphorylation and subcellular localization. EMBO J.,  2018, 37(11), e98804.
 [http://dx.doi.org/10.15252/embj.201798804] [PMID: 29764979]

[21]
Bouché, V.; Espinosa, A.P.; Leone, L.; Sardiello, M.; Ballabio, A.; Botas, J. Drosophila Mitf regulates the V-ATPase and the lysosomal-autophagic pathway. Autophagy,  2016, 12(3), 484-498.
 [http://dx.doi.org/10.1080/15548627.2015.1134081] [PMID: 26761346]

[22]
Hallsson, J.H.; Haflidadóttir, B.S.; Stivers, C.; Odenwald, W.; Arnheiter, H.; Pignoni, F.; Steingrímsson, E. The basic helix-loop-helix leucine zipper transcription factor Mitf is conserved in Drosophila and functions in eye development. Genetics,  2004, 167(1), 233-241.
 [http://dx.doi.org/10.1534/genetics.167.1.233] [PMID: 15166150]

[23]
Rehli, M.; Den Elzen, N.; Cassady, A.I.; Ostrowski, M.C.; Hume, D.A. Cloning and characterization of the murine genes for bHLH-ZIP transcription factors TFEC and TFEB reveal a common gene organization for all MiT subfamily members. Genomics,  1999, 56(1), 111-120.
 [http://dx.doi.org/10.1006/geno.1998.5588] [PMID: 10036191]

[24]
Steingrímsson, E.; Copeland, N.G.; Jenkins, N.A. Melanocytes and the microphthalmia transcription factor network. Annu. Rev. Genet.,  2004, 38(1), 365-411.
 [http://dx.doi.org/10.1146/annurev.genet.38.072902.092717] [PMID: 15568981]

[25]
Pogenberg, V.; Ballesteros-Álvarez, J.; Schober, R.; Sigvaldadóttir, I.; Obarska-Kosinska, A.; Milewski, M.; Schindl, R.; Ögmundsdóttir, M.H.; Steingrímsson, E.; Wilmanns, M. Mechanism of conditional partner selectivity in MITF/TFE family transcription factors with a conserved coiled coil stammer motif. Nucleic Acids Res.,  2020, 48(2), 934-948.
 [http://dx.doi.org/10.1093/nar/gkz1104] [PMID: 31777941]

[26]
La Spina, M.; Contreras, P.S.; Rissone, A.; Meena, N.K.; Jeong, E.; Martina, J.A. MiT/TFE Family of Transcription Factors: An Evolutionary Perspective. Front. Cell Dev. Biol.,  2021, 8609683.
 [http://dx.doi.org/10.3389/fcell.2020.609683] [PMID: 33490073]

[27]
Aksan, I.; Goding, C.R. Targeting the microphthalmia basic helix-loop-helix-leucine zipper transcription factor to a subset of E-box elements in vitro and in vivo. Mol. Cell. Biol.,  1998, 18(12), 6930-6938.
 [http://dx.doi.org/10.1128/MCB.18.12.6930] [PMID: 9819381]

[28]
Pogenberg, V.; Ögmundsdóttir, M.H.; Bergsteinsdóttir, K.; Schepsky, A.; Phung, B.; Deineko, V.; Milewski, M.; Steingrímsson, E.; Wilmanns, M. Restricted leucine zipper dimerization and specificity of DNA recognition of the melanocyte master regulator MITF. Genes Dev.,  2012, 26(23), 2647-2658.
 [http://dx.doi.org/10.1101/gad.198192.112] [PMID: 23207919]

[29]
Napolitano, G.; Esposito, A.; Choi, H.; Matarese, M.; Benedetti, V.; Di Malta, C.; Monfregola, J.; Medina, D.L.; Lippincott-Schwartz, J.; Ballabio, A. mTOR-dependent phosphorylation controls TFEB nuclear export. Nat. Commun.,  2018, 9(1), 3312.
 [http://dx.doi.org/10.1038/s41467-018-05862-6] [PMID: 30120233]

[30]
Zhao, G.Q.; Zhao, Q.; Zhou, X.; Mattei, M.G.; de Crombrugghe, B. TFEC, a basic helix-loop-helix protein, forms heterodimers with TFE3 and inhibits TFE3-dependent transcription activation. Mol. Cell. Biol.,  1993, 13(8), 4505-4512.
 [PMID: 8336698]

[31]
Martina, J.A.; Chen, Y.; Gucek, M.; Puertollano, R. MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB. Autophagy,  2012, 8(6), 903-914.
 [http://dx.doi.org/10.4161/auto.19653] [PMID: 22576015]

[32]
Chen, L.; Wang, K.; Long, A.; Jia, L.; Zhang, Y.; Deng, H.; Li, Y.; Han, J.; Wang, Y. Fasting-induced hormonal regulation of lysosomal function. Cell Res.,  2017, 27(6), 748-763.
 [http://dx.doi.org/10.1038/cr.2017.45] [PMID: 28374748]

[33]
Campbell, G.R.; Rawat, P.; Bruckman, R.S.; Spector, S.A. Human immunodeficiency virus type 1 Nef inhibits autophagy through transcription factor EB sequestration. PLoS Pathog.,  2015, 11(6), e1005018.
 [http://dx.doi.org/10.1371/journal.ppat.1005018] [PMID: 26115100]

[34]
Visvikis, O.; Ihuegbu, N.; Labed, S.A.; Luhachack, L.G.; Alves, A.M.F.; Wollenberg, A.C.; Stuart, L.M.; Stormo, G.D.; Irazoqui, J.E. Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes. Immunity,  2014, 40(6), 896-909.
 [http://dx.doi.org/10.1016/j.immuni.2014.05.002] [PMID: 24882217]

[35]
Pastore, N.; Brady, O.A.; Diab, H.I.; Martina, J.A.; Sun, L.; Huynh, T.; Lim, J.A.; Zare, H.; Raben, N.; Ballabio, A.; Puertollano, R. TFEB and TFE3 cooperate in the regulation of the innate immune response in activated macrophages. Autophagy,  2016, 12(8), 1240-1258.
 [http://dx.doi.org/10.1080/15548627.2016.1179405] [PMID: 27171064]

[36]
Gray, M.A.; Choy, C.H.; Dayam, R.M.; Ospina-Escobar, E.; Somerville, A.; Xiao, X.; Ferguson, S.M.; Botelho, R.J. Phagocytosis enhances lysosomal and bactericidal properties by activating the transcription factor TFEB. Curr. Biol.,  2016, 26(15), 1955-1964.
 [http://dx.doi.org/10.1016/j.cub.2016.05.070] [PMID: 27397893]

[37]
Nezich, C.L.; Wang, C.; Fogel, A.I.; Youle, R.J. MiT/TFE transcription factors are activated during mitophagy downstream of Parkin and Atg5. J. Cell Biol.,  2015, 210(3), 435-450.
 [http://dx.doi.org/10.1083/jcb.201501002] [PMID: 26240184]

[38]
Martina, J.A.; Diab, H.I.; Brady, O.A.; Puertollano, R. TFEB and TFE 3 are novel components of the integrated stress response. EMBO J.,  2016, 35(5), 479-495.
 [http://dx.doi.org/10.15252/embj.201593428] [PMID: 26813791]

[39]
Nardozzi, J.D.; Lott, K.; Cingolani, G. Phosphorylation meets nuclear import: a review. Cell Commun. Signal.,  2010, 8(1), 32.
 [http://dx.doi.org/10.1186/1478-811X-8-32] [PMID: 21182795]

[40]
Peña-Llopis, S.; Vega-Rubin-de-Celis, S.; Schwartz, J.C.; Wolff, N.C.; Tran, T.A.T.; Zou, L.; Xie, X.J.; Corey, D.R.; Brugarolas, J. Regulation of TFEB and V-ATPases by mTORC1. EMBO J.,  2011, 30(16), 3242-3258.
 [http://dx.doi.org/10.1038/emboj.2011.257] [PMID: 21804531]

[41]
Peña-Llopis, S.; Brugarolas, J. TFEB, a novel mTORC1 effector implicated in lysosome biogenesis, endocytosis and autophagy. Cell Cycle,  2011, 10(23), 3987-3988.
 [http://dx.doi.org/10.4161/cc.10.23.18251] [PMID: 22101272]

[42]
Szwed, A.; Kim, E.; Jacinto, E. Regulation and metabolic functions of mTORC1 and mTORC2. Physiol. Rev.,  2021, 101(3), 1371-1426.
 [http://dx.doi.org/10.1152/physrev.00026.2020] [PMID: 33599151]

[43]
Vega-Rubin-de-Celis, S.; Peña-Llopis, S.; Konda, M.; Brugarolas, J. Multistep regulation of TFEB by MTORC1. Autophagy,  2017, 13(3), 464-472.
 [http://dx.doi.org/10.1080/15548627.2016.1271514] [PMID: 28055300]

[44]
Roczniak-Ferguson, A.; Petit, C.S.; Froehlich, F.; Qian, S.; Ky, J.; Angarola, B.; Walther, T.C.; Ferguson, S.M. The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis. Sci. Signal.,  2012, 5(228), ra42.
 [http://dx.doi.org/10.1126/scisignal.2002790] [PMID: 22692423]

[45]
DeYoung, M.P.; Horak, P.; Sofer, A.; Sgroi, D.; Ellisen, L.W. Hypoxia regulates TSC1/2-mTOR signaling and tumor suppression through REDD1-mediated 14-3-3 shuttling. Genes Dev.,  2008, 22(2), 239-251.
 [http://dx.doi.org/10.1101/gad.1617608] [PMID: 18198340]

[46]
Kaper, F.; Dornhoefer, N.; Giaccia, A.J. Mutations in the PI3K/PTEN/TSC2 pathway contribute to mammalian target of rapamycin activity and increased translation under hypoxic conditions. Cancer Res.,  2006, 66(3), 1561-1569.
 [http://dx.doi.org/10.1158/0008-5472.CAN-05-3375] [PMID: 16452213]

[47]
Carling, D. AMPK signalling in health and disease. Curr. Opin. Cell Biol.,  2017, 45, 31-37.
 [http://dx.doi.org/10.1016/j.ceb.2017.01.005] [PMID: 28232179]

[48]
Paquette, M.; El-Houjeiri, L. C Zirden, L.; Puustinen, P.; Blanchette, P.; Jeong, H.; Dejgaard, K.; Siegel, P.M.; Pause, A. AMPK-dependent phosphorylation is required for transcriptional activation of TFEB and TFE3. Autophagy,  2021, 17(12), 3957-3975.
 [http://dx.doi.org/10.1080/15548627.2021.1898748] [PMID: 33734022]

[49]
Manning, B.D.; Toker, A. AKT/PKB Signaling: Navigating the Network. Cell,  2017, 169(3), 381-405.
 [http://dx.doi.org/10.1016/j.cell.2017.04.001] [PMID: 28431241]

[50]
Palmieri, M.; Pal, R.; Nelvagal, H.R.; Lotfi, P.; Stinnett, G.R.; Seymour, M.L.; Chaudhury, A.; Bajaj, L.; Bondar, V.V.; Bremner, L.; Saleem, U.; Tse, D.Y.; Sanagasetti, D.; Wu, S.M.; Neilson, J.R.; Pereira, F.A.; Pautler, R.G.; Rodney, G.G.; Cooper, J.D.; Sardiello, M. mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases. Nat. Commun.,  2017, 8, 14338.

[51]
Palmieri, M.; Pal, R.; Sardiello, M. AKT modulates the autophagy-lysosome pathway via TFEB. Cell Cycle,  2017, 16(13), 1237-1238.
 [http://dx.doi.org/10.1080/15384101.2017.1337968] [PMID: 28636416]

[52]
Li, S.; Song, Y.; Quach, C.; Guo, H.; Jang, G.B.; Maazi, H.; Zhao, S.; Sands, N.A.; Liu, Q. In, G.K.; Peng, D.; Yuan, W.; Machida, K.; Yu, M.; Akbari, O.; Hagiya, A.; Yang, Y.; Punj, V.; Tang, L.; Liang, C. Transcriptional regulation of autophagy-lysosomal function in BRAF-driven melanoma progression and chemoresistance. Nat. Commun.,  2019, 10(1), 1693.
 [http://dx.doi.org/10.1038/s41467-019-09634-8] [PMID: 30979895]

[53]
Wang, L.; Li, J.; Di, L. Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases. Med. Res. Rev.,  2022, 42(2), 946-982.
 [http://dx.doi.org/10.1002/med.21867] [PMID: 34729791]

[54]
Costa, A.; Metais, T.; Mouthon, F.; Kerkovich, D.; Charvériat, M. Evaluating and modulating TFEB in the control of autophagy: toward new treatments in CNS disorders. Fundam. Clin. Pharmacol.,  2021, 35(3), 539-551.
 [http://dx.doi.org/10.1111/fcp.12634] [PMID: 33259088]

[55]
Zhang, Y.; Wu, Z.; Huang, Z.; Liu, Y.; Chen, X.; Zhao, X.; He, H.; Deng, Y. GSK-3β inhibition elicits a neuroprotection by restoring lysosomal dysfunction in neurons via facilitation of TFEB nuclear translocation after ischemic stroke. Brain Res.,  2022, 1778147768.
 [http://dx.doi.org/10.1016/j.brainres.2021.147768] [PMID: 34968440]

[56]
Li, Y.; Xu, M.; Ding, X.; Yan, C.; Song, Z.; Chen, L.; Huang, X.; Wang, X.; Jian, Y.; Tang, G.; Tang, C.; Di, Y.; Mu, S.; Liu, X.; Liu, K.; Li, T.; Wang, Y.; Miao, L.; Guo, W.; Hao, X.; Yang, C. Protein kinase C controls lysosome biogenesis independently of mTORC1. Nat. Cell Biol.,  2016, 18(10), 1065-1077.
 [http://dx.doi.org/10.1038/ncb3407] [PMID: 27617930]

[57]
Ferron, M.; Settembre, C.; Shimazu, J.; Lacombe, J.; Kato, S.; Rawlings, D.J.; Ballabio, A.; Karsenty, G. A RANKL-PKCβ-TFEB signaling cascade is necessary for lysosomal biogenesis in osteoclasts. Genes Dev.,  2013, 27(8), 955-969.
 [http://dx.doi.org/10.1101/gad.213827.113] [PMID: 23599343]

[58]
Tong, Y.; Song, F. Intracellular calcium signaling regulates autophagy via calcineurin-mediated TFEB dephosphorylation. Autophagy,  2015, 11(7), 1192-1195.
 [http://dx.doi.org/10.1080/15548627.2015.1054594] [PMID: 26043755]

[59]
Medina, D.L.; Di Paola, S.; Peluso, I.; Armani, A.; De Stefani, D.; Venditti, R.; Montefusco, S.; Scotto-Rosato, A.; Prezioso, C.; Forrester, A.; Settembre, C.; Wang, W.; Gao, Q.; Xu, H.; Sandri, M.; Rizzuto, R.; De Matteis, M.A.; Ballabio, A. Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. Nat. Cell Biol.,  2015, 17(3), 288-299.
 [http://dx.doi.org/10.1038/ncb3114] [PMID: 25720963]

[60]
Silvestrini, M.J.; Johnson, J.R.; Kumar, A.V.; Thakurta, T.G.; Blais, K.; Neill, Z.A.; Marion, S.W.; St Amand, V.; Reenan, R.A.; Lapierre, L.R. Nuclear Export Inhibition Enhances HLH-30/TFEB Activity, Autophagy, and Lifespan. Cell Rep.,  2018, 23(7), 1915-1921.
 [http://dx.doi.org/10.1016/j.celrep.2018.04.063] [PMID: 29768192]

[61]
Li, L.; Friedrichsen, H.J.; Andrews, S.; Picaud, S.; Volpon, L.; Ngeow, K.; Berridge, G.; Fischer, R.; Borden, K.L.B.; Filippakopoulos, P.; Goding, C.R. A TFEB nuclear export signal integrates amino acid supply and glucose availability. Nat. Commun.,  2018, 9(1), 2685.
 [http://dx.doi.org/10.1038/s41467-018-04849-7] [PMID: 29992949]

[62]
Kırlı, K.; Karaca, S.; Dehne, H.J.; Samwer, M.; Pan, K.T.; Lenz, C.; Urlaub, H.; Görlich, D. A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. eLife,  2015, 4, e11466.
 [http://dx.doi.org/10.7554/eLife.11466] [PMID: 26673895]

[63]
Yang, M.; Zhang, Y.; Ren, J. Acetylation in cardiovascular diseases: Molecular mechanisms and clinical implications. Biochim. Biophys. Acta Mol. Basis Dis.,  2020, 1866(10), 165836.
 [http://dx.doi.org/10.1016/j.bbadis.2020.165836] [PMID: 32413386]

[64]
Wang, Y.; Huang, Y.; Liu, J.; Zhang, J.; Xu, M.; You, Z.; Peng, C.; Gong, Z.; Liu, W. Acetyltransferase GCN5 regulates autophagy and lysosome biogenesis by targeting TFEB. EMBO Rep.,  2020, 21(1), e48335.
 [http://dx.doi.org/10.15252/embr.201948335] [PMID: 31750630]

[65]
Bao, J.; Zheng, L.; Zhang, Q.; Li, X.; Zhang, X.; Li, Z.; Bai, X.; Zhang, Z.; Huo, W.; Zhao, X.; Shang, S.; Wang, Q.; Zhang, C.; Ji, J. Deacetylation of TFEB promotes fibrillar Aβ degradation by upregulating lysosomal biogenesis in microglia. Protein Cell,  2016, 7(6), 417-433.
 [http://dx.doi.org/10.1007/s13238-016-0269-2] [PMID: 27209302]

[66]
Brijmohan, A.S.; Batchu, S.N.; Majumder, S.; Alghamdi, T.A.; Thieme, K.; McGaugh, S.; Liu, Y.; Advani, S.L.; Bowskill, B.B.; Kabir, M.G.; Geldenhuys, L.; Siddiqi, F.S.; Advani, A. HDAC6 inhibition promotes transcription factor EB activation and is protective in experimental kidney disease. Front. Pharmacol.,  2018, 9, 34.
 [http://dx.doi.org/10.3389/fphar.2018.00034] [PMID: 29449811]

[67]
Meacham, G.C.; Patterson, C.; Zhang, W.; Younger, J.M.; Cyr, D.M. The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation. Nat. Cell Biol.,  2001, 3(1), 100-105.
 [http://dx.doi.org/10.1038/35050509] [PMID: 11146634]

[68]
Rao, L.; Sha, Y.; Eissa, N.T. The E3 ubiquitin ligase STUB1 regulates autophagy and mitochondrial biogenesis by modulating TFEB activity. Mol. Cell. Oncol.,  2017, 4(6), e1372867.
 [http://dx.doi.org/10.1080/23723556.2017.1372867] [PMID: 29209655]

[69]
Sha, Y.; Rao, L.; Settembre, C.; Ballabio, A.; Eissa, N.T. STUB 1 regulates TFEB‐induced autophagy-lysosome pathway. EMBO J.,  2017, 36(17), 2544-2552.
 [http://dx.doi.org/10.15252/embj.201796699] [PMID: 28754656]

[70]
Lipton, P. Ischemic cell death in brain neurons. Physiol. Rev.,  1999, 79(4), 1431-1568.
 [http://dx.doi.org/10.1152/physrev.1999.79.4.1431] [PMID: 10508238]

[71]
Bonora, M.; Patergnani, S.; Rimessi, A.; De Marchi, E.; Suski, J.M.; Bononi, A.; Giorgi, C.; Marchi, S.; Missiroli, S.; Poletti, F.; Wieckowski, M.R.; Pinton, P. ATP synthesis and storage. Purinergic Signal.,  2012, 8(3), 343-357.
 [http://dx.doi.org/10.1007/s11302-012-9305-8] [PMID: 22528680]

[72]
Tuo, Q.; Zhang, S.; Lei, P. Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications. Med. Res. Rev.,  2022, 42(1), 259-305.
 [http://dx.doi.org/10.1002/med.21817] [PMID: 33957000]

[73]
Back, T.; Hemmen, T.; Schüler, O.G. Lesion evolution in cerebral ischemia. J. Neurol.,  2004, 251(4), 388-397.
 [http://dx.doi.org/10.1007/s00415-004-0399-y] [PMID: 15083282]

[74]
Sifat, A.E.; Nozohouri, S.; Archie, S.R.; Chowdhury, E.A.; Abbruscato, T.J. Brain energy metabolism in ischemic stroke: Effects of smoking and diabetes. Int. J. Mol. Sci.,  2022, 23(15), 8512.
 [http://dx.doi.org/10.3390/ijms23158512] [PMID: 35955647]

[75]
Oakhill, J.S.; Steel, R.; Chen, Z.P.; Scott, J.W.; Ling, N.; Tam, S.; Kemp, B.E. AMPK is a direct adenylate charge-regulated protein kinase. Science,  2011, 332(6036), 1433-1435.
 [http://dx.doi.org/10.1126/science.1200094] [PMID: 21680840]

[76]
Chun, Y.; Kim, J. AMPK-mTOR signaling and cellular adaptations in hypoxia. Int. J. Mol. Sci.,  2021, 22(18), 9765.
 [http://dx.doi.org/10.3390/ijms22189765] [PMID: 34575924]

[77]
Inoki, K.; Ouyang, H.; Zhu, T.; Lindvall, C.; Wang, Y.; Zhang, X.; Yang, Q.; Bennett, C.; Harada, Y.; Stankunas, K.; Wang, C.; He, X.; MacDougald, O.A.; You, M.; Williams, B.O.; Guan, K.L. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell,  2006, 126(5), 955-968.
 [http://dx.doi.org/10.1016/j.cell.2006.06.055] [PMID: 16959574]

[78]
Folbergrová, J.; Memezawa, H.; Smith, M.L.; Siesjö, B.K. Focal and perifocal changes in tissue energy state during middle cerebral artery occlusion in normo- and hyperglycemic rats. J. Cereb. Blood Flow Metab.,  1992, 12(1), 25-33.
 [http://dx.doi.org/10.1038/jcbfm.1992.4] [PMID: 1727140]

[79]
Paschen, W.; Oláh, L.; Mies, G. Effect of transient focal ischemia of mouse brain on energy state and NAD levels: no evidence that NAD depletion plays a major role in secondary disturbances of energy metabolism. J. Neurochem.,  2000, 75(4), 1675-1680.
 [http://dx.doi.org/10.1046/j.1471-4159.2000.0751675.x] [PMID: 10987849]

[80]
Zoncu, R.; Bar-Peled, L.; Efeyan, A.; Wang, S.; Sancak, Y.; Sabatini, D.M. mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. Science,  2011, 334(6056), 678-683.
 [http://dx.doi.org/10.1126/science.1207056] [PMID: 22053050]

[81]
Sancak, Y.; Bar-Peled, L.; Zoncu, R.; Markhard, A.L.; Nada, S.; Sabatini, D.M. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell,  2010, 141(2), 290-303.
 [http://dx.doi.org/10.1016/j.cell.2010.02.024] [PMID: 20381137]

[82]
Sancak, Y.; Peterson, T.R.; Shaul, Y.D.; Lindquist, R.A.; Thoreen, C.C.; Bar-Peled, L.; Sabatini, D.M. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science,  2008, 320(5882), 1496-1501.
 [http://dx.doi.org/10.1126/science.1157535] [PMID: 18497260]

[83]
Bar-Peled, L.; Schweitzer, L.D.; Zoncu, R.; Sabatini, D.M. Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. Cell,  2012, 150(6), 1196-1208.
 [http://dx.doi.org/10.1016/j.cell.2012.07.032] [PMID: 22980980]

[84]
Martina, J.A.; Puertollano, R. Rag GTPases mediate amino acid-dependent recruitment of TFEB and MITF to lysosomes. J. Cell Biol.,  2013, 200(4), 475-491.
 [http://dx.doi.org/10.1083/jcb.201209135] [PMID: 23401004]

[85]
Saucedo, L.J.; Gao, X.; Chiarelli, D.A.; Li, L.; Pan, D.; Edgar, B.A. Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat. Cell Biol.,  2003, 5(6), 566-571.
 [http://dx.doi.org/10.1038/ncb996] [PMID: 12766776]

[86]
Martina, J.A.; Diab, H.I.; Lishu, L.; Jeong-A, L.; Patange, S.; Raben, N.; Puertollano, R. The nutrient-responsive transcription factor TFE3 promotes autophagy, lysosomal biogenesis, and clearance of cellular debris. Sci. Signal.,  2014, 7(309), ra9.
 [http://dx.doi.org/10.1126/scisignal.2004754] [PMID: 24448649]

[87]
Settembre, C.; Zoncu, R.; Medina, D.L.; Vetrini, F.; Erdin, S.; Erdin, S.; Huynh, T.; Ferron, M.; Karsenty, G.; Vellard, M.C.; Facchinetti, V.; Sabatini, D.M.; Ballabio, A. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J.,  2012, 31(5), 1095-1108.
 [http://dx.doi.org/10.1038/emboj.2012.32] [PMID: 22343943]

[88]
Tsun, Z.Y.; Bar-Peled, L.; Chantranupong, L.; Zoncu, R.; Wang, T.; Kim, C.; Spooner, E.; Sabatini, D.M. The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1. Mol. Cell,  2013, 52(4), 495-505.
 [http://dx.doi.org/10.1016/j.molcel.2013.09.016] [PMID: 24095279]

[89]
Dibble, C.C.; Elis, W.; Menon, S.; Qin, W.; Klekota, J.; Asara, J.M.; Finan, P.M.; Kwiatkowski, D.J.; Murphy, L.O.; Manning, B.D. TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1. Mol. Cell,  2012, 47(4), 535-546.
 [http://dx.doi.org/10.1016/j.molcel.2012.06.009] [PMID: 22795129]

[90]
Raben, N.; Puertollano, R. TFEB and TFE3: Linking lysosomes to cellular adaptation to stress. Annu. Rev. Cell Dev. Biol.,  2016, 32(1), 255-278.
 [http://dx.doi.org/10.1146/annurev-cellbio-111315-125407] [PMID: 27298091]

[91]
Evans, T.D.; Zhang, X.; Jeong, S.J.; He, A.; Song, E.; Bhattacharya, S.; Holloway, K.B.; Lodhi, I.J.; Razani, B. TFEB drives PGC-1α expression in adipocytes to protect against diet-induced metabolic dysfunction. Sci. Signal.,  2019, 12(606), eaau2281.
 [http://dx.doi.org/10.1126/scisignal.aau2281] [PMID: 31690633]

[92]
Chen, D.; Xie, J.; Fiskesund, R.; Dong, W.; Liang, X.; Lv, J.; Jin, X.; Liu, J.; Mo, S.; Zhang, T.; Cheng, F.; Zhou, Y.; Zhang, H.; Tang, K.; Ma, J.; Liu, Y.; Huang, B. Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype. Nat. Commun.,  2018, 9(1), 873.
 [http://dx.doi.org/10.1038/s41467-018-03225-9] [PMID: 29491374]

[93]
Zhang, X.; Wei, M.; Fan, J.; Yan, W.; Zha, X.; Song, H.; Wan, R.; Yin, Y.; Wang, W. Ischemia-induced upregulation of autophagy preludes dysfunctional lysosomal storage and associated synaptic impairments in neurons. Autophagy,  2021, 17(6), 1519-1542.
 [http://dx.doi.org/10.1080/15548627.2020.1840796] [PMID: 33111641]

[94]
Yang, Y.; Lv, S.Y.; Lyu, S.K.; Wu, D.; Chen, Q. The protective effect of apelin on ischemia/reperfusion injury. Peptides,  2015, 63, 43-46.
 [http://dx.doi.org/10.1016/j.peptides.2014.11.001] [PMID: 25447414]

[95]
Wang, P.; Shao, B.Z.; Deng, Z.; Chen, S.; Yue, Z.; Miao, C.Y. Autophagy in ischemic stroke. Prog. Neurobiol.,  2018, 163-164, 98-117.
 [http://dx.doi.org/10.1016/j.pneurobio.2018.01.001] [PMID: 29331396]

[96]
Sun, Y.L.; Zhu, Y.H.; Zhong, X.J.; Chen, X.L.; Wang, J.; Ying, G.Z. Crosstalk between autophagy and cerebral ischemia. Front. Neurosci.,  2019, 12, 1022.
 [http://dx.doi.org/10.3389/fnins.2018.01022] [PMID: 30692904]

[97]
Ravikumar, B.; Sarkar, S.; Davies, J.E.; Futter, M.; Garcia-Arencibia, M.; Green-Thompson, Z.W.; Jimenez-Sanchez, M.; Korolchuk, V.I.; Lichtenberg, M.; Luo, S.; Massey, D.C.O.; Menzies, F.M.; Moreau, K.; Narayanan, U.; Renna, M.; Siddiqi, F.H.; Underwood, B.R.; Winslow, A.R.; Rubinsztein, D.C. Regulation of mammalian autophagy in physiology and pathophysiology. Physiol. Rev.,  2010, 90(4), 1383-1435.
 [http://dx.doi.org/10.1152/physrev.00030.2009] [PMID: 20959619]

[98]
Liu, Y.; Xue, X.; Zhang, H.; Che, X.; Luo, J.; Wang, P.; Xu, J.; Xing, Z.; Yuan, L.; Liu, Y.; Fu, X.; Su, D.; Sun, S.; Zhang, H.; Wu, C.; Yang, J. Neuronal-targeted TFEB rescues dysfunction of the autophagy-lysosomal pathway and alleviates ischemic injury in permanent cerebral ischemia. Autophagy,  2019, 15(3), 493-509.
 [http://dx.doi.org/10.1080/15548627.2018.1531196] [PMID: 30304977]

[99]
Chen, J.H.; Kuo, H.C.; Lee, K.F.; Tsai, T.H. Global proteomic analysis of brain tissues in transient ischemia brain damage in rats. Int. J. Mol. Sci.,  2015, 16(12), 11873-11891.
 [http://dx.doi.org/10.3390/ijms160611873] [PMID: 26016499]

[100]
Ahsan, A.; Zheng, Y.; Ma, S.; Liu, M.; Cao, M.; Li, Y.; Zheng, W.; Zhou, X.; Xin, M.; Hu, W.; Chen, Z.; Zhang, X. Tomatidine protects against ischemic neuronal injury by improving lysosomal function. Eur. J. Pharmacol.,  2020, 882173280.
 [http://dx.doi.org/10.1016/j.ejphar.2020.173280] [PMID: 32580039]

[101]
Hossain, M.I.; Marcus, J.M.; Lee, J.H.; Garcia, P.L.; Singh, V.; Shacka, J.J.; Zhang, J.; Gropen, T.I.; Falany, C.N.; Andrabi, S.A. Restoration of CTSD (cathepsin D) and lysosomal function in stroke is neuroprotective. Autophagy,  2021, 17(6), 1330-1348.
 [http://dx.doi.org/10.1080/15548627.2020.1761219] [PMID: 32450052]

[102]
Bajaj, L.; Lotfi, P.; Pal, R.; Ronza, A.; Sharma, J.; Sardiello, M. Lysosome biogenesis in health and disease. J. Neurochem.,  2019, 148(5), 573-589.
 [http://dx.doi.org/10.1111/jnc.14564] [PMID: 30092616]

[103]
Wu, Z.; Zhang, Y.; Liu, Y.; Chen, X.; Huang, Z.; Zhao, X.; He, H.; Deng, Y. Melibiose confers a neuroprotection against cerebral ischemia/reperfusion injury by ameliorating autophagy flux via facilitation of TFEB nuclear translocation in neurons. Life (Basel),  2021, 11(9), 948.
 [http://dx.doi.org/10.3390/life11090948] [PMID: 34575099]

[104]
Fu, X.; Liu, Y.; Zhang, H.; Yu, X.; Wang, X.; Wu, C.; Yang, J. Pseudoginsenoside F11 ameliorates the dysfunction of the autophagy-lysosomal pathway by activating calcineurin-mediated TFEB nuclear translocation in neuron during permanent cerebral ischemia. Exp. Neurol.,  2021, 338113598.
 [http://dx.doi.org/10.1016/j.expneurol.2021.113598] [PMID: 33422553]

[105]
Judge, A.; Dodd, M.S. Metabolism. Essays Biochem.,  2020, 64(4), 607-647.
 [http://dx.doi.org/10.1042/EBC20190041] [PMID: 32830223]

[106]
Pastore, N.; Vainshtein, A.; Klisch, T.J.; Armani, A.; Huynh, T.; Herz, N.J.; Polishchuk, E.V.; Sandri, M.; Ballabio, A. TFE 3 regulates whole‐body energy metabolism in cooperation with TFEB. EMBO Mol. Med.,  2017, 9(5), 605-621.
 [http://dx.doi.org/10.15252/emmm.201607204] [PMID: 28283651]

[107]
Smith, R.A.J.; Hartley, R.C.; Cochemé, H.M.; Murphy, M.P. Mitochondrial pharmacology. Trends Pharmacol. Sci.,  2012, 33(6), 341-352.
 [http://dx.doi.org/10.1016/j.tips.2012.03.010] [PMID: 22521106]

[108]
Zeng, M.; He, Y.; Du, H.; Yang, J.; Wan, H. Output regulation and function optimization of mitochondria in eukaryotes. Front. Cell Dev. Biol.,  2020, 8, 598112.
 [http://dx.doi.org/10.3389/fcell.2020.598112] [PMID: 33330486]

[109]
Cunnane, S.C.; Trushina, E.; Morland, C.; Prigione, A.; Casadesus, G.; Andrews, Z.B.; Beal, M.F.; Bergersen, L.H.; Brinton, R.D.; de la Monte, S.; Eckert, A.; Harvey, J.; Jeggo, R.; Jhamandas, J.H.; Kann, O.; la Cour, C.M.; Martin, W.F.; Mithieux, G.; Moreira, P.I.; Murphy, M.P.; Nave, K.A.; Nuriel, T.; Oliet, S.H.R.; Saudou, F.; Mattson, M.P.; Swerdlow, R.H.; Millan, M.J. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat. Rev. Drug Discov.,  2020, 19(9), 609-633.
 [http://dx.doi.org/10.1038/s41573-020-0072-x] [PMID: 32709961]

[110]
Alano, C.C.; Garnier, P.; Ying, W.; Higashi, Y.; Kauppinen, T.M.; Swanson, R.A. NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal death. J. Neurosci.,  2010, 30(8), 2967-2978.
 [http://dx.doi.org/10.1523/JNEUROSCI.5552-09.2010] [PMID: 20181594]

[111]
Sun, J.; Lu, H.; Liang, W.; Zhao, G.; Ren, L.; Hu, D.; Chang, Z.; Liu, Y.; Garcia-Barrio, M.T.; Zhang, J.; Chen, Y.E.; Fan, Y. Endothelial TFEB (transcription factor EB) improves glucose tolerance via upregulation of IRS (insulin receptor substrate) 1 and IRS2. Arterioscler. Thromb. Vasc. Biol.,  2021, 41(2), 783-795.
 [http://dx.doi.org/10.1161/ATVBAHA.120.315310] [PMID: 33297755]

[112]
Li, Y.; Ma, Z.; Jiang, S.; Hu, W.; Li, T.; Di, S.; Wang, D.; Yang, Y. A global perspective on FOXO1 in lipid metabolism and lipid-related diseases. Prog. Lipid Res.,  2017, 66, 42-49.
 [http://dx.doi.org/10.1016/j.plipres.2017.04.002] [PMID: 28392404]

[113]
Thomes, P.G.; Rasineni, K.; Yang, L.; Donohue, T.M., Jr; Kubik, J.L.; McNiven, M.A.; Casey, C.A. Ethanol withdrawal mitigates fatty liver by normalizing lipid catabolism. Am. J. Physiol. Gastrointest. Liver Physiol.,  2019, 316(4), G509-G518.
 [http://dx.doi.org/10.1152/ajpgi.00376.2018] [PMID: 30714813]

[114]
Zechner, R.; Zimmermann, R.; Eichmann, T.O.; Kohlwein, S.D.; Haemmerle, G.; Lass, A.; Madeo, F. FAT SIGNALS-lipases and lipolysis in lipid metabolism and signaling. Cell Metab.,  2012, 15(3), 279-291.
 [http://dx.doi.org/10.1016/j.cmet.2011.12.018] [PMID: 22405066]

[115]
Martinez-Lopez, N.; Singh, R. Autophagy and lipid droplets in the liver. Annu. Rev. Nutr.,  2015, 35(1), 215-237.
 [http://dx.doi.org/10.1146/annurev-nutr-071813-105336] [PMID: 26076903]

[116]
Chen, K.; Yuan, R.; Zhang, Y.; Geng, S.; Li, L. Tollip deficiency alters atherosclerosis and steatosis by disrupting lipophagy. J. Am. Heart Assoc.,  2017, 6(4), e004078.
 [http://dx.doi.org/10.1161/JAHA.116.004078] [PMID: 28396568]

[117]
Lundquist, M.R.; Goncalves, M.D.; Loughran, R.M.; Possik, E.; Vijayaraghavan, T.; Yang, A.; Pauli, C.; Ravi, A.; Verma, A.; Yang, Z.; Johnson, J.L.; Wong, J.C.Y.; Ma, Y.; Hwang, K.S.K.; Weinkove, D.; Divecha, N.; Asara, J.M.; Elemento, O.; Rubin, M.A.; Kimmelman, A.C.; Pause, A.; Cantley, L.C.; Emerling, B.M. Phosphatidylinositol-5-phosphate 4-kinases regulate cellular lipid metabolism by facilitating autophagy. Mol. Cell,  2018, 70(3), 531-544.e9.
 [http://dx.doi.org/10.1016/j.molcel.2018.03.037] [PMID: 29727621]

[118]
Ye, M.; Zhou, J.; Zhong, Y.; Xu, J.; Hou, J.; Wang, X.; Wang, Z.; Guo, D. SR-A-Targeted phase-transition nanoparticles for the detection and treatment of atherosclerotic vulnerable plaques. ACS Appl. Mater. Interfaces,  2019, 11(10), 9702-9715.
 [http://dx.doi.org/10.1021/acsami.8b18190] [PMID: 30785263]

[119]
Zhu, Z.D.; Yu, T.; Liu, H.J.; Jin, J.; He, J. SOCE induced calcium overload regulates autophagy in acute pancreatitis via calcineurin activation. Cell Death Dis.,  2018, 9(2), 50.
 [http://dx.doi.org/10.1038/s41419-017-0073-9] [PMID: 29352220]

[120]
Maus, M.; Cuk, M.; Patel, B.; Lian, J.; Ouimet, M.; Kaufmann, U.; Yang, J.; Horvath, R.; Hornig-Do, H.T.; Chrzanowska-Lightowlers, Z.M.; Moore, K.J.; Cuervo, A.M.; Feske, S. Store-operated Ca2+ entry controls induction of lipolysis and the transcriptional reprogramming to lipid metabolism. Cell Metab.,  2017, 25(3), 698-712.
 [http://dx.doi.org/10.1016/j.cmet.2016.12.021] [PMID: 28132808]

[121]
Rutkai, I.; Merdzo, I.; Wunnava, S.V.; Curtin, G.T.; Katakam, P.V.G.; Busija, D.W. Cerebrovascular function and mitochondrial bioenergetics after ischemia-reperfusion in male rats. J. Cereb. Blood Flow Metab.,  2019, 39(6), 1056-1068.
 [http://dx.doi.org/10.1177/0271678X17745028] [PMID: 29215305]

[122]
Anderson, M.F.; Sims, N.R. Mitochondrial respiratory function and cell death in focal cerebral ischemia. J. Neurochem.,  1999, 73(3), 1189-1199.
 [http://dx.doi.org/10.1046/j.1471-4159.1999.0731189.x] [PMID: 10461911]

[123]
Chouchani, E.T.; Pell, V.R.; James, A.M.; Work, L.M.; Saeb-Parsy, K.; Frezza, C.; Krieg, T.; Murphy, M.P. A unifying mechanism for mitochondrial superoxide production during ischemia-reperfusion injury. Cell Metab.,  2016, 23(2), 254-263.
 [http://dx.doi.org/10.1016/j.cmet.2015.12.009] [PMID: 26777689]

[124]
An, H.; Zhou, B.; Ji, X. Mitochondrial quality control in acute ischemic stroke. J. Cereb. Blood Flow Metab.,  2021, 41(12), 3157-3170.
 [http://dx.doi.org/10.1177/0271678X211046992] [PMID: 34551609]

[125]
Chan, D.C. Fusion and fission: interlinked processes critical for mitochondrial health. Annu. Rev. Genet.,  2012, 46(1), 265-287.
 [http://dx.doi.org/10.1146/annurev-genet-110410-132529] [PMID: 22934639]

[126]
Chen, Z.; Li, Y.; Wang, Y.; Qian, J.; Ma, H.; Wang, X.; Jiang, G.; Liu, M.; An, Y.; Ma, L.; Kang, L.; Jia, J.; Yang, C.; Zhang, G.; Chen, Y.; Gao, W.; Fu, M.; Huang, Z.; Tang, H.; Zhu, Y.; Ge, J.; Gong, H.; Zou, Y. Cardiomyocyte-restricted low density lipoprotein receptor-related protein 6 (LRP6) deletion leads to lethal dilated cardiomyopathy partly through Drp1 signaling. Theranostics,  2018, 8(3), 627-643.
 [http://dx.doi.org/10.7150/thno.22177] [PMID: 29344294]

[127]
Ryter, S.W.; Bhatia, D.; Choi, M.E. Autophagy: A lysosome-dependent process with implications in cellular redox homeostasis and human disease. Antioxid. Redox Signal.,  2019, 30(1), 138-159.
 [http://dx.doi.org/10.1089/ars.2018.7518] [PMID: 29463101]

[128]
Ivankovic, D.; Chau, K.Y.; Schapira, A.H.V.; Gegg, M.E. Mitochondrial and lysosomal biogenesis are activated following] PINK 1/parkin‐mediated mitophagy. J. Neurochem.,  2016, 136(2), 388-402.
 [http://dx.doi.org/10.1111/jnc.13412] [PMID: 26509433]

[129]
Settembre, C.; De Cegli, R.; Mansueto, G.; Saha, P.K.; Vetrini, F.; Visvikis, O.; Huynh, T.; Carissimo, A.; Palmer, D.; Jürgen Klisch, T.; Wollenberg, A.C.; Di Bernardo, D.; Chan, L.; Irazoqui, J.E.; Ballabio, A. TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nat. Cell Biol.,  2013, 15(6), 647-658.
 [http://dx.doi.org/10.1038/ncb2718] [PMID: 23604321]

[130]
Wu, L.; Wang, R. Carbon monoxide: endogenous production, physiological functions, and pharmacological applications. Pharmacol. Rev.,  2005, 57(4), 585-630.
 [http://dx.doi.org/10.1124/pr.57.4.3] [PMID: 16382109]

[131]
Shi, H. Hypoxia inducible factor 1 as a therapeutic target in ischemic stroke. Curr. Med. Chem.,  2009, 16(34), 4593-4600.
 [http://dx.doi.org/10.2174/092986709789760779] [PMID: 19903149]

[132]
Kim, H.J.; Joe, Y.; Rah, S.Y.; Kim, S.K.; Park, S.U.; Park, J.; Kim, J.; Ryu, J.; Cho, G.J.; Surh, Y.J.; Ryter, S.W.; Kim, U.H.; Chung, H.T. Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury. Cell Death Dis.,  2018, 9(11), 1060.
 [http://dx.doi.org/10.1038/s41419-018-1112-x] [PMID: 30333475]

[133]
Saito, A.; Maier, C.M.; Narasimhan, P.; Nishi, T.; Song, Y.S.; Yu, F.; Liu, J.; Lee, Y.S.; Nito, C.; Kamada, H.; Dodd, R.L.; Hsieh, L.B.; Hassid, B.; Kim, E.E.; González, M.; Chan, P.H. Oxidative stress and neuronal death/survival signaling in cerebral ischemia. Mol. Neurobiol.,  2005, 31(1-3), 105-116.
 [http://dx.doi.org/10.1385/MN:31:1-3:105] [PMID: 15953815]

[134]
Zhang, P.; Cui, J. Neuroprotective effect of fisetin against the cerebral ischemia-reperfusion damage via suppression of oxidative stress and inflammatory parameters. Inflammation,  2021, 44(4), 1490-1506.
 [http://dx.doi.org/10.1007/s10753-021-01434-x] [PMID: 33616827]

[135]
Martina, J.A.; Puertollano, R. Protein phosphatase 2A stimulates activation of TFEB and TFE3 transcription factors in response to oxidative stress. J. Biol. Chem.,  2018, 293(32), 12525-12534.
 [http://dx.doi.org/10.1074/jbc.RA118.003471] [PMID: 29945972]

[136]
Yang, Z.; Huang, C.; Wu, Y.; Chen, B.; Zhang, W.; Zhang, J. Autophagy protects the blood-brain barrier through regulating the dynamic of claudin-5 in short-term starvation. Front. Physiol.,  2019, 10, 2.
 [http://dx.doi.org/10.3389/fphys.2019.00002] [PMID: 30713499]

[137]
Campanella, M.; Klionsky, D.J. Keeping the engine clean. Autophagy,  2013, 9(11), 1647-1647.
 [http://dx.doi.org/10.4161/auto.26915] [PMID: 24162014]

[138]
Yamamoto, M.; Kensler, T.W.; Motohashi, H. The KEAP1-NRF2 system: A thiol-based sensor-effector apparatus for maintaining redox homeostasis. Physiol. Rev.,  2018, 98(3), 1169-1203.
 [http://dx.doi.org/10.1152/physrev.00023.2017] [PMID: 29717933]

[139]
Li, D.; Shao, R.; Wang, N.; Zhou, N.; Du, K.; Shi, J.; Wang, Y.; Zhao, Z.; Ye, X.; Zhang, X.; Xu, H. Sulforaphane Activates a lysosome-dependent transcriptional program to mitigate oxidative stress. Autophagy,  2021, 17(4), 872-887.
 [http://dx.doi.org/10.1080/15548627.2020.1739442] [PMID: 32138578]

[140]
Lyman, M.; Lloyd, D.G.; Ji, X.; Vizcaychipi, M.P.; Ma, D. Neuroinflammation: The role and consequences. Neurosci. Res.,  2014, 79, 1-12.
 [http://dx.doi.org/10.1016/j.neures.2013.10.004] [PMID: 24144733]

[141]
Gaire, B.P. Microglia as the critical regulators of neuroprotection and functional recovery in cerebral ischemia. Cell. Mol. Neurobiol., 2021.
 [PMID: 34460037]

[142]
Michinaga, S.; Koyama, Y. Pathophysiological responses and roles of astrocytes in traumatic brain injury. Int. J. Mol. Sci.,  2021, 22(12), 6418.
 [http://dx.doi.org/10.3390/ijms22126418] [PMID: 34203960]

[143]
Chen, Y.J.; Nguyen, H.M.; Maezawa, I.; Grössinger, E.M.; Garing, A.L.; Köhler, R.; Jin, L.W.; Wulff, H. The potassium channel KCa3.1 constitutes a pharmacological target for neuroinflammation associated with ischemia/reperfusion stroke. J. Cereb. Blood Flow Metab.,  2016, 36(12), 2146-2161.
 [http://dx.doi.org/10.1177/0271678X15611434] [PMID: 26661208]

[144]
Lawrence, T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb. Perspect. Biol.,  2009, 1(6), a001651.
 [http://dx.doi.org/10.1101/cshperspect.a001651] [PMID: 20457564]

[145]
Wang, X.; Wang, Q.; Li, W.; Zhang, Q.; Jiang, Y.; Guo, D.; Sun, X.; Lu, W.; Li, C.; Wang, Y. TFEB-NF-κB inflammatory signaling axis: a novel therapeutic pathway of Dihydrotanshinone I in doxorubicin-induced cardiotoxicity. J. Exp. Clin. Cancer Res.,  2020, 39(1), 93.
 [http://dx.doi.org/10.1186/s13046-020-01595-x] [PMID: 32448281]

[146]
Song, W.; Zhang, C.L.; Gou, L.; He, L.; Gong, Y.Y.; Qu, D.; Zhao, L.; Jin, N.; Chan, T.F.; Wang, L.; Tian, X.Y.; Luo, J.Y.; Huang, Y. Endothelial TFEB (Transcription Factor EB) Restrains IKK (IκB Kinase)-p65 Pathway to Attenuate Vascular Inflammation in Diabetic db/db Mice. Arterioscler. Thromb. Vasc. Biol.,  2019, 39(4), 719-730.
 [http://dx.doi.org/10.1161/ATVBAHA.119.312316] [PMID: 30816805]

[147]
Gong, Z.; Pan, J.R.; Shen, Q.Y.; Li, M.; Peng, Y. Mitochondrial dysfunction induces NLRP3 inflammasome activation during cerebral ischemia/reperfusion injury. J. Neuroinflammation,  2018, 15(1), 242.
 [http://dx.doi.org/10.1186/s12974-018-1282-6] [PMID: 30153825]

[148]
Biasizzo, M.; Kopitar-Jerala, N. Interplay Between NLRP3 Inflammasome and Autophagy. Front. Immunol.,  2020, 11591803.
 [http://dx.doi.org/10.3389/fimmu.2020.591803] [PMID: 33163006]

[149]
Nakahira, K.; Haspel, J.A.; Rathinam, V.A.K.; Lee, S.J.; Dolinay, T.; Lam, H.C.; Englert, J.A.; Rabinovitch, M.; Cernadas, M.; Kim, H.P.; Fitzgerald, K.A.; Ryter, S.W.; Choi, A.M.K. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat. Immunol.,  2011, 12(3), 222-230.
 [http://dx.doi.org/10.1038/ni.1980] [PMID: 21151103]

[150]
Chen, J.; Mao, K.; Yu, H.; Wen, Y.; She, H.; Zhang, H.; Liu, L.; Li, M.; Li, W.; Zou, F. p38-TFEB pathways promote microglia activation through inhibiting CMA-mediated NLRP3 degradation in Parkinson’s disease. J. Neuroinflammation,  2021, 18(1), 295.
 [http://dx.doi.org/10.1186/s12974-021-02349-y] [PMID: 34930303]

[151]
Shi, C.S.; Shenderov, K.; Huang, N.N.; Kabat, J.; Abu-Asab, M.; Fitzgerald, K.A.; Sher, A.; Kehrl, J.H. Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction. Nat. Immunol.,  2012, 13(3), 255-263.
 [http://dx.doi.org/10.1038/ni.2215] [PMID: 22286270]

[152]
Harris, J.; Hartman, M.; Roche, C.; Zeng, S.G.; O’Shea, A.; Sharp, F.A.; Lambe, E.M.; Creagh, E.M.; Golenbock, D.T.; Tschopp, J.; Kornfeld, H.; Fitzgerald, K.A.; Lavelle, E.C. Autophagy controls IL-1beta secretion by targeting pro-IL-1beta for degradation. J. Biol. Chem.,  2011, 286(11), 9587-9597.
 [http://dx.doi.org/10.1074/jbc.M110.202911] [PMID: 21228274]

[153]
Linnik, M.D.; Zobrist, R.H.; Hatfield, M.D. Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats. Stroke,  1993, 24(12), 2002-2008.
 [http://dx.doi.org/10.1161/01.STR.24.12.2002] [PMID: 8248983]

[154]
Radak, D.; Katsiki, N.; Resanovic, I.; Jovanovic, A.; Sudar-Milovanovic, E.; Zafirovic, S.; Mousad, S.A.; Isenovic, E.R. Apoptosis and Acute Brain Ischemia in Ischemic Stroke. Curr. Vasc. Pharmacol.,  2017, 15(2), 115-122.
 [http://dx.doi.org/10.2174/1570161115666161104095522] [PMID: 27823556]

[155]
Wang, R.; Dong, Y.; Lu, Y.; Zhang, W.; Brann, D.W.; Zhang, Q. Photobiomodulation for global cerebral ischemia: Targeting mitochondrial dynamics and functions. Mol. Neurobiol.,  2019, 56(3), 1852-1869.
 [http://dx.doi.org/10.1007/s12035-018-1191-9] [PMID: 29951942]

[156]
Landshamer, S.; Hoehn, M.; Barth, N.; Duvezin-Caubet, S.; Schwake, G.; Tobaben, S.; Kazhdan, I.; Becattini, B.; Zahler, S.; Vollmar, A.; Pellecchia, M.; Reichert, A.; Plesnila, N.; Wagner, E.; Culmsee, C. Bid-induced release of AIF from mitochondria causes immediate neuronal cell death. Cell Death Differ.,  2008, 15(10), 1553-1563.
 [http://dx.doi.org/10.1038/cdd.2008.78] [PMID: 18535584]

[157]
Culmsee, C.; Krieglstein, J. Ischaemic brain damage after stroke: new insights into efficient therapeutic strategies. EMBO Rep.,  2007, 8(2), 129-133.
 [http://dx.doi.org/10.1038/sj.embor.7400892] [PMID: 17218952]

[158]
Szabó, M.R.; Pipicz, M.; Csont, T.; Csonka, C. Modulatory effect of myokines on reactive oxygen species in ischemia/reperfusion. Int. J. Mol. Sci.,  2020, 21(24), 9382.
 [http://dx.doi.org/10.3390/ijms21249382] [PMID: 33317180]

[159]
Martin-Villalba, A.; Herr, I.; Jeremias, I.; Hahne, M.; Brandt, R.; Vogel, J.; Schenkel, J.; Herdegen, T.; Debatin, K.M. CD95 ligand (Fas-L/APO-1L) and tumor necrosis factor-related apoptosis-inducing ligand mediate ischemia-induced apoptosis in neurons. J. Neurosci.,  1999, 19(10), 3809-3817.
 [http://dx.doi.org/10.1523/JNEUROSCI.19-10-03809.1999] [PMID: 10234013]

[160]
Muhammad, I.F.; Borné, Y.; Melander, O.; Orho-Melander, M.; Nilsson, J.; Söderholm, M.; Engström, G. FADD (fas-associated protein with death domain), caspase-3, and caspase-8 and incidence of ischemic stroke. Stroke,  2018, 49(9), 2224-2226.
 [http://dx.doi.org/10.1161/STROKEAHA.118.022063] [PMID: 30354994]

[161]
Morita-Fujimura, Y.; Fujimura, M.; Yoshimoto, T.; Chan, P.H. Superoxide during reperfusion contributes to caspase-8 expression and apoptosis after transient focal stroke. Stroke,  2001, 32(10), 2356-2361.
 [http://dx.doi.org/10.1161/hs1001.097241] [PMID: 11588326]

[162]
Plesnila, N.; Zinkel, S.; Le, D.A.; Amin-Hanjani, S.; Wu, Y.; Qiu, J.; Chiarugi, A.; Thomas, S.S.; Kohane, D.S.; Korsmeyer, S.J.; Moskowitz, M.A. BID mediates neuronal cell death after oxygen/glucose deprivation and focal cerebral ischemia. Proc. Natl. Acad. Sci. USA,  2001, 98(26), 15318-15323.
 [http://dx.doi.org/10.1073/pnas.261323298] [PMID: 11742085]

[163]
Yonekawa, T.; Gamez, G.; Kim, J.; Tan, A.C.; Thorburn, J.; Gump, J.; Thorburn, A.; Morgan, M.J. RIP 1 negatively regulates basal autophagic flux through TFEB to control sensitivity to apoptosis. EMBO Rep.,  2015, 16(6), 700-708.
 [http://dx.doi.org/10.15252/embr.201439496] [PMID: 25908842]

[164]
Lu, H.; Sun, J.; Liang, W.; Chang, Z.; Rom, O.; Zhao, Y.; Zhao, G.; Xiong, W.; Wang, H.; Zhu, T.; Guo, Y.; Chang, L.; Garcia-Barrio, M.T.; Zhang, J.; Chen, Y.E.; Fan, Y. Cyclodextrin prevents abdominal aortic aneurysm via activation of vascular smooth muscle cell transcription factor EB. Circulation,  2020, 142(5), 483-498.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044803] [PMID: 32354235]

[165]
Krupinski, J.; Kaluza, J.; Kumar, P.; Wang, M.; Kumar, S. Prognostic value of blood vessel density in ischaemic stroke. Lancet,  1993, 342(8873), 742.
 [http://dx.doi.org/10.1016/0140-6736(93)91734-4] [PMID: 8103843]

[166]
Steingrímsson, E.; Tessarollo, L.; Reid, S.W.; Jenkins, N.A.; Copeland, N.G. The bHLH-Zip transcription factor Tfeb is essential for placental vascularization. Development,  1998, 125(23), 4607-4616.
 [http://dx.doi.org/10.1242/dev.125.23.4607] [PMID: 9806910]

[167]
Doronzo, G.; Astanina, E.; Corà, D.; Chiabotto, G.; Comunanza, V.; Noghero, A.; Neri, F.; Puliafito, A.; Primo, L.; Spampanato, C.; Settembre, C.; Ballabio, A.; Camussi, G.; Oliviero, S.; Bussolino, F. TFEB controls vascular development by regulating the proliferation of endothelial cells. EMBO J.,  2019, 38(3), e98250.
 [http://dx.doi.org/10.15252/embj.201798250] [PMID: 30591554]

[168]
Wang, L.; Xiong, X.; Zhang, L.; Shen, J. Neurovascular Unit: A critical role in ischemic stroke. CNS Neurosci. Ther.,  2021, 27(1), 7-16.
 [http://dx.doi.org/10.1111/cns.13561] [PMID: 33389780]

[169]
Davis, C.; Savitz, S.I.; Satani, N. Mesenchymal stem cell derived extracellular vesicles for repairing the neurovascular unit after ischemic stroke. Cells,  2021, 10(4), 767.
 [http://dx.doi.org/10.3390/cells10040767] [PMID: 33807314]

[170]
Du, H.; Xu, Y.; Zhu, L. Role of semaphorins in ischemic stroke. Front. Mol. Neurosci.,  2022, 15, 848506.
 [http://dx.doi.org/10.3389/fnmol.2022.848506] [PMID: 35350431]

[171]
Eroglu, C.; Barres, B.A. Regulation of synaptic connectivity by glia. Nature,  2010, 468(7321), 223-231.
 [http://dx.doi.org/10.1038/nature09612] [PMID: 21068831]

[172]
Beard, E.; Lengacher, S.; Dias, S.; Magistretti, P.J.; Finsterwald, C. Astrocytes as key regulators of brain energy metabolism: New therapeutic perspectives. Front. Physiol.,  2022, 12825816.
 [http://dx.doi.org/10.3389/fphys.2021.825816] [PMID: 35087428]

[173]
Guo, H.; Zhang, Z.; Gu, T.; Yu, D.; Shi, Y.; Gao, Z.; Wang, Z.; Liu, W.; Fan, Z.; Hou, W.; Wang, H.; Cai, Y. Astrocytic glycogen mobilization participates in salvianolic acid B-mediated neuroprotection against reperfusion injury after ischemic stroke. Exp. Neurol.,  2022, 349, 113966.
 [http://dx.doi.org/10.1016/j.expneurol.2021.113966] [PMID: 34973964]

[174]
Bednarski, E.; Lauterborn, J.C.; Gall, C.M.; Lynch, G. Lysosomal dysfunction reduces brain-derived neurotrophic factor expression. Exp. Neurol.,  1998, 150(1), 128-135.
 [http://dx.doi.org/10.1006/exnr.1997.6747] [PMID: 9514826]

[175]
Di Malta, C.; Fryer, J.D.; Settembre, C.; Ballabio, A. Astrocyte dysfunction triggers neurodegeneration in a lysosomal storage disorder. Proc. Natl. Acad. Sci. USA,  2012, 109(35), E2334-E2342.
 [http://dx.doi.org/10.1073/pnas.1209577109] [PMID: 22826245]

[176]
Lee, J.W.; Nam, H.; Kim, L.E.; Jeon, Y.; Min, H.; Ha, S.; Lee, Y.; Kim, S.Y.; Lee, S.J.; Kim, E.K.; Yu, S.W. TLR4 (toll-like receptor 4) activation suppresses autophagy through inhibition of FOXO3 and impairs phagocytic capacity of microglia. Autophagy,  2019, 15(5), 753-770.
 [http://dx.doi.org/10.1080/15548627.2018.1556946] [PMID: 30523761]

[177]
Saab, A.S.; Nave, K.A. Myelin dynamics: Protecting and shaping neuronal functions. Curr. Opin. Neurobiol.,  2017, 47, 104-112.
 [http://dx.doi.org/10.1016/j.conb.2017.09.013] [PMID: 29065345]

[178]
Garcia-Martin, G.; Alcover-Sanchez, B.; Wandosell, F.; Cubelos, B. Pathways involved in remyelination after cerebral ischemia. Curr. Neuropharmacol.,  2022, 20(4), 751-765.
 [http://dx.doi.org/10.2174/1570159X19666210610093658] [PMID: 34151767]

[179]
Sun, L.O.; Mulinyawe, S.B.; Collins, H.Y.; Ibrahim, A.; Li, Q.; Simon, D.J.; Tessier-Lavigne, M.; Barres, B.A. Spatiotemporal control of CNS myelination by oligodendrocyte programmed cell death through the TFEB-PUMA Axis. Cell,  2018, 175(7), 1811-1826.e21.
 [http://dx.doi.org/10.1016/j.cell.2018.10.044] [PMID: 30503207]

[180]
Meireles, A.M.; Shen, K.; Zoupi, L.; Iyer, H.; Bouchard, E.L.; Williams, A.; Talbot, W.S. The lysosomal transcription factor TFEB represses myelination downstream of the rag-ragulator complex. Dev. Cell,  2018, 47(3), 319-330.e5.
 [http://dx.doi.org/10.1016/j.devcel.2018.10.003] [PMID: 30399334]

[181]
Duchemin, S.; Boily, M.; Sadekova, N.; Girouard, H. The complex contribution of NOS interneurons in the physiology of cerebrovascular regulation. Front. Neural Circuits,  2012, 6, 51.
 [http://dx.doi.org/10.3389/fncir.2012.00051] [PMID: 22907993]

[182]
Yoo, J.; Jeong, I.K.; Ahn, K.J.; Chung, H.Y.; Hwang, Y.C. Fenofibrate, a PPARα agonist, reduces hepatic fat accumulation through the upregulation of TFEB-mediated lipophagy. Metabolism,  2021, 120, 154798.
 [http://dx.doi.org/10.1016/j.metabol.2021.154798] [PMID: 33984335]

[183]
Fang, Y.; Ji, L.; Zhu, C.; Xiao, Y.; Zhang, J.; Lu, J.; Yin, J.; Wei, L. Liraglutide alleviates hepatic steatosis by activating the TFEB-regulated autophagy-lysosomal pathway. Front. Cell Dev. Biol.,  2020, 8, 602574.
 [http://dx.doi.org/10.3389/fcell.2020.602574] [PMID: 33330497]

[184]
Wu, H.; Ding, J.; Li, S.; Lin, J.; Jiang, R.; Lin, C.; Dai, L.; Xie, C.; Lin, D.; Xu, H.; Gao, W.; Zhou, K. Metformin promotes the survival of random-pattern skin flaps by inducing autophagy via the AMPK-mTOR-TFEB signaling pathway. Int. J. Biol. Sci.,  2019, 15(2), 325-340.
 [http://dx.doi.org/10.7150/ijbs.29009] [PMID: 30745824]

[185]
Chandra, S.; Jana, M.; Pahan, K. Aspirin induces lysosomal biogenesis and attenuates amyloid plaque pathology in a mouse model of Alzheimer’s disease via PPARα. J. Neurosci.,  2018, 38(30), 6682-6699.
 [http://dx.doi.org/10.1523/JNEUROSCI.0054-18.2018] [PMID: 29967008]

[186]
Li, J.; Xiang, X.; Xu, Z. Cilostazol protects against myocardial ischemia and reperfusion injury by activating transcription factor EB (TFEB). Biotechnol. Appl. Biochem.,  2019, 66(4), 555-563.
 [http://dx.doi.org/10.1002/bab.1754] [PMID: 30994947]

[187]
Bhogal, P.; Brouwer, P.A.; Makalanda, H.L.D. Cilostazol: an antiplatelet agent for the neurointerventionist? J. Neurointerv. Surg.,  2016, 8(2), 208-209.
 [http://dx.doi.org/10.1136/neurintsurg-2014-011570] [PMID: 25526917]

[188]
Zhang, W.; Wang, J.; Yang, C. Celastrol, a TFEB (transcription factor EB) agonist, is a promising drug candidate for Alzheimer disease. Autophagy,  2022, 18(7), 1740-1742.
 [http://dx.doi.org/10.1080/15548627.2022.2046437] [PMID: 35253615]

[189]
Rusmini, P.; Cortese, K.; Crippa, V.; Cristofani, R.; Cicardi, M.E.; Ferrari, V.; Vezzoli, G.; Tedesco, B.; Meroni, M.; Messi, E.; Piccolella, M.; Galbiati, M.; Garrè, M.; Morelli, E.; Vaccari, T.; Poletti, A. Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of motoneuron degeneration. Autophagy,  2019, 15(4), 631-651.
 [http://dx.doi.org/10.1080/15548627.2018.1535292] [PMID: 30335591]

[190]
Moskot, M.; Montefusco, S.; Jakóbkiewicz-Banecka, J.; Mozolewski, P.; Węgrzyn, A.; Di Bernardo, D.; Węgrzyn, G.; Medina, D.L.; Ballabio, A.; Gabig-Cimińska, M. The phytoestrogen genistein modulates lysosomal metabolism and transcription factor EB (TFEB) activation. J. Biol. Chem.,  2014, 289(24), 17054-17069.
 [http://dx.doi.org/10.1074/jbc.M114.555300] [PMID: 24770416]

[191]
Jia, Y.; Zhang, L.; Liu, Z.; Mao, C.; Ma, Z.; Li, W.; Yu, F.; Wang, Y.; Huang, Y.; Zhang, W.; Zheng, J.; Wang, X.; Xu, Q.; Zhang, J.; Feng, W.; Yun, C.; Liu, C.; Sun, J.; Fu, Y.; Cui, Q.; Kong, W. Targeting macrophage TFEB-14-3-3 epsilon interface by naringenin inhibits abdominal aortic aneurysm. Cell Discov.,  2022, 8(1), 21.
 [http://dx.doi.org/10.1038/s41421-021-00363-1] [PMID: 35228523]

[192]
Song, J.X.; Sun, Y.R.; Peluso, I.; Zeng, Y.; Yu, X.; Lu, J.H.; Xu, Z.; Wang, M.Z.; Liu, L.F.; Huang, Y.Y.; Chen, L.L.; Durairajan, S.S.K.; Zhang, H.J.; Zhou, B.; Zhang, H.Q.; Lu, A.; Ballabio, A.; Medina, D.L.; Guo, Z.; Li, M. A novel curcumin analog binds to and activates TFEB in vitro and in vivo independent of MTOR inhibition. Autophagy,  2016, 12(8), 1372-1389.
 [http://dx.doi.org/10.1080/15548627.2016.1179404] [PMID: 27172265]

[193]
Cao, S.; Wang, C.; Yan, J.; Li, X.; Wen, J.; Hu, C. Curcumin ameliorates oxidative stress-induced intestinal barrier injury and mitochondrial damage by promoting Parkin dependent mitophagy through AMPK-TFEB signal pathway. Free Radic. Biol. Med.,  2020, 147, 8-22.
 [http://dx.doi.org/10.1016/j.freeradbiomed.2019.12.004] [PMID: 31816386]

[194]
Si, Q.; Wu, G.; Cao, X. Effects of electroacupuncture on acute cerebral infarction. Acupunct. Electrother. Res.,  1998, 23(2), 117-124.
 [http://dx.doi.org/10.3727/036012998816356562] [PMID: 9789586]

[195]
Xiong, L.; Lu, Z.; Hou, L.; Zheng, H.; Zhu, Z.; Wang, Q.; Chen, S. Pretreatment with repeated electroacupuncture attenuates transient focal cerebral ischemic injury in rats. Chin. Med. J. (Engl.),  2003, 116(1), 108-111.
 [PMID: 12667400]

[196]
Jing, L.; Zonglu, B.; Yuanhao, D.; Yongfeng, L.; Xuezhu, Z.; Bo, P.; Jingjing, Z.; Li, Y. Effect of Electroacupuncture on expression of Ang/Tie-2 mRNA and protein in rats with acute cerebral infarction. J. Tradit. Chin. Med.,  2017, 37(5), 659-666.
 [http://dx.doi.org/10.1016/S0254-6272(17)30320-5] [PMID: 32188227]

[197]
Zheng, X.; Lin, W.; Jiang, Y.; Lu, K.; Wei, W.; Huo, Q.; Cui, S.; Yang, X.; Li, M.; Xu, N.; Tang, C.; Song, J.X. Electroacupuncture ameliorates beta-amyloid pathology and cognitive impairment in Alzheimer disease via a novel mechanism involving activation of TFEB (transcription factor EB). Autophagy,  2021, 17(11), 3833-3847.
 [http://dx.doi.org/10.1080/15548627.2021.1886720] [PMID: 33622188]

[198]
Zheng, G.; Chen, B.; Fang, Q.; Yi, H.; Lin, Q.; Chen, L.; Tao, J.; Li, J.; Zheng, X.; Li, M.; Lan, X. Primary prevention for risk factors of ischemic stroke with Baduanjin exercise intervention in the community elder population: Study protocol for a randomized controlled trial. Trials,  2014, 15(1), 113.
 [http://dx.doi.org/10.1186/1745-6215-15-113] [PMID: 24712684]

[199]
Yasuhara, T.; Anthony, S.S.; Date, I. Limiting exercise inhibits neuronal recovery from neurological disorders. Brain Circ.,  2017, 3(3), 124-129.
 [http://dx.doi.org/10.4103/bc.bc_16_17] [PMID: 30276313]

[200]
Zhang, Y.; Zhang, P.; Shen, X.; Tian, S.; Wu, Y.; Zhu, Y.; Jia, J.; Wu, J.; Hu, Y. Early exercise protects the blood-brain barrier from ischemic brain injury via the regulation of MMP-9 and occludin in rats. Int. J. Mol. Sci.,  2013, 14(6), 11096-11112.
 [http://dx.doi.org/10.3390/ijms140611096] [PMID: 23708107]

[201]
Terashi, T.; Otsuka, S.; Takada, S.; Nakanishi, K.; Ueda, K.; Sumizono, M.; Kikuchi, K.; Sakakima, H. Neuroprotective effects of different frequency preconditioning exercise on neuronal apoptosis after focal brain ischemia in rats. Neurol. Res.,  2019, 41(6), 510-518.
 [http://dx.doi.org/10.1080/01616412.2019.1580458] [PMID: 30822224]

[202]
Bernhardt, J.; Langhorne, P.; Lindley, R.I.; Thrift, A.G.; Ellery, F.; Collier, J.; Churilov, L.; Moodie, M.; Dewey, H.; Donnan, G.; Grp, A.T.C. Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial. Lancet,  2015, 386(9988), 46-55.
 [http://dx.doi.org/10.1016/S0140-6736(15)60690-0] [PMID: 25892679]

[203]
MacKay-Lyons, M.; Billinger, S.A.; Eng, J.J.; Dromerick, A.; Giacomantonio, N.; Hafer-Macko, C.; Macko, R.; Nguyen, E.; Prior, P.; Suskin, N.; Tang, A.; Thornton, M.; Unsworth, K. Aerobic Exercise Recommendations to Optimize Best Practices in Care After Stroke: AEROBICS 2019 Update. Phys. Ther.,  2020, 100(1), 149-156.
 [http://dx.doi.org/10.1093/ptj/pzz153] [PMID: 31596465]

[204]
Huang, J.; Wang, X.; Zhu, Y.; Li, Z.; Zhu, Y.T.; Wu, J.C.; Qin, Z.H.; Xiang, M.; Lin, F. Exercise activates lysosomal function in the brain through AMPK‐SIRT1‐TFEB pathway. CNS Neurosci. Ther.,  2019, 25(6), 796-807.
 [http://dx.doi.org/10.1111/cns.13114] [PMID: 30864262]

[205]
Wang, X.; Zhu, Y.T.; Zhu, Y.; Sun, Y.L.; Huang, J.; Li, Z.; Wang, Y.; Wu, J.C.; Qin, Z.H.; Lin, F. Long-term running exercise alleviates cognitive dysfunction in APP/PSEN1 transgenic mice via enhancing brain lysosomal function. Acta Pharmacol. Sin., 2021.
 [PMID: 34272505]

[206]
Li, Z.; Cui, X.; Lv, H.; Liu, J.; Di, W.; Jiang, F.; Liu, Y.; Cheng, X. Remote ischemic postconditioning attenuates damage in rats with chronic cerebral ischemia by upregulating the autophagolysosome pathway via the activation of TFEB. Exp. Mol. Pathol.,  2020, 115, 104475.
 [http://dx.doi.org/10.1016/j.yexmp.2020.104475] [PMID: 32473154]

[207]
He, W.; Wang, H.; Zhao, C.; Tian, X.; Li, L.; Wang, H. Role of liraglutide in brain repair promotion through Sirt1‐mediated mitochondrial improvement in stroke. J. Cell. Physiol.,  2020, 235(3), 2986-3001.
 [http://dx.doi.org/10.1002/jcp.29204] [PMID: 31535381]

[208]
Tu, W.J.; Zeng, Q.J.; Wang, K.; Wang, Y.; Sun, B.L.; Zeng, X.W.; Liu, Q. Prestroke metformin use on the 1-year prognosis of intracerebral hemorrhage patients with type 2 diabetes. Oxid. Med. Cell. Longev.,  2021, 2021, 2027359.
 [http://dx.doi.org/10.1155/2021/2027359] [PMID: 34567407]

[209]
Gautier, S.; Ouk, T.; Petrault, M.; Petrault, O.; Berezowski, V.; Bordet, R. PPAR-Alpha agonist used at the acute phase of experimental ischemic stroke reduces occurrence of thrombolysis-induced hemorrhage in rats. PPAR Res.,  2015, 2015, 246329.
 [http://dx.doi.org/10.1155/2015/246329] [PMID: 26106408]

[210]
Toyoda, K.; Omae, K.; Hoshino, H.; Uchiyama, S.; Kimura, K.; Miwa, K.; Minematsu, K.; Yamaguchi, K.; Suda, Y.; Toru, S.; Kitagawa, K.; Ihara, M.; Koga, M.; Yamaguchi, T. Association of timing for starting dual antiplatelet treatment with cilostazol and recurrent stroke. Neurology,  2022, 98(10), e983-e992.
 [http://dx.doi.org/10.1212/WNL.0000000000200064] [PMID: 35074890]

[211]
Chen, J.; Ji, L.; Tong, X.; Han, M.; Zhao, S.; Qin, Y.; He, Z.; Jiang, Z.; Liu, A. Economic evaluation of ticagrelor plus aspirin versus aspirin alone for acute ischemic stroke and transient ischemic attack. Front. Pharmacol.,  2022, 13, 790048.
 [http://dx.doi.org/10.3389/fphar.2022.790048] [PMID: 35370758]

[212]
Wang, C.; Niederstrasser, H.; Douglas, P.M.; Lin, R.; Jaramillo, J.; Li, Y.; Oswald, N.W.; Zhou, A.; McMillan, E.A.; Mendiratta, S.; Wang, Z.; Zhao, T.; Lin, Z.; Luo, M.; Huang, G.; Brekken, R.A.; Posner, B.A.; MacMillan, J.B.; Gao, J.; White, M.A. Small-molecule TFEB pathway agonists that ameliorate metabolic syndrome in mice and extend C. elegans lifespan. Nat. Commun.,  2017, 8(1), 2270.
 [http://dx.doi.org/10.1038/s41467-017-02332-3] [PMID: 29273768]

[213]
Lai, K.C.; Chen, S.J.; Lin, C.S.; Yang, F.C.; Lin, C.L.; Hsu, C.W.; Huang, W.C.; Kao, C.H. Digoxin and amiodarone on the risk of ischemic stroke in atrial fibrillation: An observational study. Front. Pharmacol.,  2018, 9, 448.
 [http://dx.doi.org/10.3389/fphar.2018.00448] [PMID: 29867460]

[214]
Li, Z.W.; Cui, X.L.; Lv, H.; Liu, J.; Di, W.; Jiang, F.; Liu, Y.; Cheng, X.S. Remote ischemic postconditioning attenuates damage in rats with chronic cerebral ischemia by upregulating the autophagolysosome pathway via the activation of TFEB (vol 115, 104475, 2020). Exp. Mol. Pathol.,  2021, 121.

[215]
Wang, M.; Ran, Q.; Chen, H.; Liu, Y.; Yu, H.; Shi, F. Electroacupuncture preconditioning attenuates ischemic brain injury by activation of the adenosine monophosphate-activated protein kinase signaling pathway. Neural Regen. Res.,  2015, 10(7), 1069-1075.
 [http://dx.doi.org/10.4103/1673-5374.160095] [PMID: 26330828]

[216]
Dornbos, D., III; Zwagerman, N.; Guo, M.; Ding, J.Y.; Peng, C.; Esmail, F.; Sikharam, C.; Geng, X.; Guthikonda, M.; Ding, Y. Preischemic exercise reduces brain damage by ameliorating metabolic disorder in ischemia/reperfusion injury. J. Neurosci. Res.,  2013, 91(6), 818-827.
 [http://dx.doi.org/10.1002/jnr.23203] [PMID: 23553672]

[217]
Tsao, C.W.; Aday, A.W.; Almarzooq, Z.I.; Alonso, A.; Beaton, A.Z.; Bittencourt, M.S.; Boehme, A.K.; Buxton, A.E.; Carson, A.P.; Commodore-Mensah, Y.; Elkind, M.S.V.; Evenson, K.R.; Eze-Nliam, C.; Ferguson, J.F.; Generoso, G.; Ho, J.E.; Kalani, R.; Khan, S.S.; Kissela, B.M.; Knutson, K.L.; Levine, D.A.; Lewis, T.T.; Liu, J.; Loop, M.S.; Ma, J.; Mussolino, M.E.; Navaneethan, S.D.; Perak, A.M.; Poudel, R.; Rezk-Hanna, M.; Roth, G.A.; Schroeder, E.B.; Shah, S.H.; Thacker, E.L.; VanWagner, L.B.; Virani, S.S.; Voecks, J.H.; Wang, N.Y.; Yaffe, K.; Martin, S.S. Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association. Circulation,  2022, 145(8), e153-e639.
 [http://dx.doi.org/10.1161/CIR.0000000000001052] [PMID: 35078371]

[218]
Dong, X. Current strategies for brain drug delivery. Theranostics,  2018, 8(6), 1481-1493.
 [http://dx.doi.org/10.7150/thno.21254] [PMID: 29556336]
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DOI https://dx.doi.org/10.2174/1570159X21666230724095558	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190
Current Neuropharmacology

Transcription Factor EB: A Promising Therapeutic Target for Ischemic Stroke

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