Login Register Cart 0
Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
General Review Article

Post-Translational Modifications of BACE1 in Alzheimer's Disease

Author(s): Wen Wen, Ping Li, Panwang Liu, Shijun Xu*, Fushun Wang* and Jason H Huang

Volume 20, Issue 1, 2022

Page: [211 - 222] Pages: 12

DOI: 10.2174/1570159X19666210121163224

Price: $65

conference banner
Abstract

Beta-Amyloid Cleaving Enzyme1 (BACE1) is a monospecific enzyme for the key ratelimiting step in the synthesis of beta-amyloid(Aβ) from cleavage of amyloid precursor protein (APP), to form senile plaques and causes cognitive dysfunction in Alzheimer's disease (AD). Post-translation modifications of BACE1, such as acetylation, glycosylation, palmitoylation, phosphorylation, play a crucial role in the trafficking and maturation process of BACE1. The study of BACE1 is of great importance not only for understanding the formation of toxic Aβ but also for the development of an effective therapeutic target for the treatment of AD. This paper review recent advances in the studies about BACE1, with focuses being paid to the relationship of Aβ, BACE1 with posttranslational regulation of BACE1. In addition, we specially reviewed studies about the compounds that can be used to affect post-translational regulation of BACE1 or regulate BACE1 in the literature, which can be used for subsequent research on whether BACE1 is a post-translationally modified drug.

Keywords: Alzheimer`s disease, APP, Aβ, BACE1, neurodegenerative diseases, post-translational modification.

« Previous Next »
Graphical Abstract

[1]
Group, G.N.D.C. Global, regional, and national burden of neurological disorders during 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol., 2017, 16(11), 877-897.
[2]
Hou, Y.; Dan, X.; Babbar, M.; Wei, Y.; Hasselbalch, S.G.; Croteau, D.L.; Bohr, V.A. Ageing as a risk factor for neurodegenerative disease. Nat. Rev. Neurol., 2019, 15(10), 565-581.
[http://dx.doi.org/10.1038/s41582-019-0244-7] [PMID: 31501588]
[3]
Wang, X.; Huang, W.; Su, L.; Xing, Y.; Jessen, F.; Sun, Y.; Shu, N.; Han, Y. Neuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer’s disease. Mol. Neurodegener., 2020, 15(1), 55.
[http://dx.doi.org/10.1186/s13024-020-00395-3] [PMID: 32962744]
[4]
Reynolds, D.S. A short perspective on the long road to effective treatments for Alzheimer’s disease. Br. J. Pharmacol., 2019, 176(18), 3636-3648.
[http://dx.doi.org/10.1111/bph.14581] [PMID: 30657599]
[5]
Chen, G.F.; Xu, T.H.; Yan, Y.; Zhou, Y.R.; Jiang, Y.; Melcher, K.; Xu, H.E. Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacol. Sin., 2017, 38(9), 1205-1235.
[http://dx.doi.org/10.1038/aps.2017.28] [PMID: 28713158]
[6]
Jamerlan, A.; An, S.S.A.; Hulme, J. Advances in amyloid beta oligomer detection applications in Alzheimer’s disease. Trends Analyt. Chem., 2020, 129, 115919.
[http://dx.doi.org/10.1016/j.trac.2020.115919]
[7]
Hane, F.T.; Robinson, M.; Lee, B.Y.; Bai, O.; Leonenko, Z.; Albert, M.S. Recent Progress in Alzheimer’s disease research, Part 3: diagnosis and treatment. J. Alzheimers Dis., 2017, 57(3), 645-665.
[http://dx.doi.org/10.3233/JAD-160907] [PMID: 28269772]
[8]
Brati, D.; Riqiang, Yan. A close look at BACE1 inhibitors for Alzheimer’s disease treatment. CNS Drugs, 2019, 33(3), 251-263.
[9]
Panza, F.; Lozupone, M.; Logroscino, G.; Imbimbo, B.P. A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nat. Rev. Neurol., 2019, 15(2), 73-88.
[http://dx.doi.org/10.1038/s41582-018-0116-6] [PMID: 30610216]
[10]
Scopa, C.; Marrocco, F.; Latina, V.; Ruggeri, F.; Corvaglia, V.; La Regina, F.; Ammassari-Teule, M.; Middei, S.; Amadoro, G.; Meli, G.; Scardigli, R.; Cattaneo, A. Impaired adult neurogenesis is an early event in Alzheimer’s disease neurodegeneration, mediated by intracellular Aβ oligomers. Cell Death Differ., 2020, 27(3), 934-948.
[http://dx.doi.org/10.1038/s41418-019-0409-3] [PMID: 31591472]
[11]
Cline, E.N.; Bicca, M.A.; Viola, K.L.; Klein, W.L. The amyloid-β oligomer hypothesis: beginning of the third decade. J. Alzheimers Dis., 2018, 64(s1), S567-S610.
[http://dx.doi.org/10.3233/JAD-179941] [PMID: 29843241]
[12]
Araki, W. Post-translational regulation of the β-secretase BACE1. Brain Res. Bull., 2016, 126(Pt 2), 170-177.
[http://dx.doi.org/10.1016/j.brainresbull.2016.04.009] [PMID: 27086128]
[13]
Kagan, B.L.; Jang, H.; Capone, R.; Teran Arce, F.; Ramachandran, S.; Lal, R.; Nussinov, R. Antimicrobial properties of amyloid peptides. Mol. Pharm., 2012, 9(4), 708-717.
[http://dx.doi.org/10.1021/mp200419b] [PMID: 22081976]
[14]
Kumar, D.K.; Choi, S.H.; Washicosky, K.J.; Eimer, W.A.; Tucker, S.; Ghofrani, J.; Lefkowitz, A.; McColl, G.; Goldstein, L.E.; Tanzi, R.E.; Moir, R.D. Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease. Sci. Transl. Med., 2016, 8(340), 340ra72.
[http://dx.doi.org/10.1126/scitranslmed.aaf1059] [PMID: 27225182]
[15]
Soscia, S.J.; Kirby, J.E.; Washicosky, K.J.; Tucker, S.M.; Ingelsson, M.; Hyman, B.; Burton, M.A.; Goldstein, L.E.; Duong, S.; Tanzi, R.E.; Moir, R.D. The Alzheimer’s disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One, 2010, 5(3), e9505.
[http://dx.doi.org/10.1371/journal.pone.0009505] [PMID: 20209079]
[16]
Reinholz, M.; Ruzicka, T.; Schauber, J. Cathelicidin LL-37: an antimicrobial peptide with a role in inflammatory skin disease. Ann. Dermatol., 2012, 24(2), 126-135.
[http://dx.doi.org/10.5021/ad.2012.24.2.126] [PMID: 22577261]
[17]
Cao, Y.; Chtarbanova, S.; Petersen, A.J.; Ganetzky, B. Dnr1 mutations cause neurodegeneration in Drosophila by activating the innate immune response in the brain. Proc. Natl. Acad. Sci. USA, 2013, 110(19), E1752-E1760.
[http://dx.doi.org/10.1073/pnas.1306220110] [PMID: 23613578]
[18]
Takahashi, R.H.; Nagao, T.; Gouras, G.K. Plaque formation and the intraneuronal accumulation of β-amyloid in Alzheimer’s disease. Pathol. Int., 2017, 67(4), 185-193.
[http://dx.doi.org/10.1111/pin.12520] [PMID: 28261941]
[19]
Ashe, K.H. The biogenesis and biology of amyloid β oligomers in the brain. Alzheimers Dement., 2020, 16(11), 1561-1567.
[http://dx.doi.org/10.1002/alz.12084] [PMID: 32543725]
[20]
Lee, S.J.; Nam, E.; Lee, H.J.; Savelieff, M.G.; Lim, M.H. Towards an understanding of amyloid-β oligomers: characterization, toxicity mechanisms, and inhibitors. Chem. Soc. Rev., 2017, 46(2), 310-323.
[http://dx.doi.org/10.1039/C6CS00731G] [PMID: 27878186]
[21]
Um, J.W.; Nygaard, H.B.; Heiss, J.K.; Kostylev, M.A.; Stagi, M.; Vortmeyer, A.; Wisniewski, T.; Gunther, E.C.; Strittmatter, S.M. Alzheimer amyloid-β oligomer bound to postsynaptic prion protein activates Fyn to impair neurons. Nat. Neurosci., 2012, 15(9), 1227-1235.
[http://dx.doi.org/10.1038/nn.3178] [PMID: 22820466]
[22]
Viola, K.L.; Klein, W.L. Amyloid β oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis. Acta Neuropathol., 2015, 129(2), 183-206.
[http://dx.doi.org/10.1007/s00401-015-1386-3] [PMID: 25604547]
[23]
Economou, N.J.; Giammona, M.J.; Do, T.D.; Zheng, X.; Teplow, D.B.; Buratto, S.K.; Bowers, M.T. Amyloid β-protein assembly and Alzheimer’s disease: dodecamers of Aβ42, but Not of Aβ40, seed fibril formation. J. Am. Chem. Soc., 2016, 138(6), 1772-1775.
[http://dx.doi.org/10.1021/jacs.5b11913] [PMID: 26839237]
[24]
Moraes, B.J.; Coelho, P.; Fão, L.; Ferreira, I.L.; Rego, A.C. Modified glutamatergic postsynapse in neurodegenerative disorders. Neuroscience, 2021, 454, 116-139.
[PMID: 31887357]
[25]
Talantova, M.; Sanz-Blasco, S.; Zhang, X.; Xia, P.; Akhtar, M.W.; Okamoto, S.; Dziewczapolski, G.; Nakamura, T.; Cao, G.; Pratt, A.E.; Kang, Y.J.; Tu, S.; Molokanova, E.; McKercher, S.R.; Hires, S.A.; Sason, H.; Stouffer, D.G.; Buczynski, M.W.; Solomon, J.P.; Michael, S.; Powers, E.T.; Kelly, J.W.; Roberts, A.; Tong, G.; Fang-Newmeyer, T.; Parker, J.; Holland, E.A.; Zhang, D.; Nakanishi, N.; Chen, H.S.; Wolosker, H.; Wang, Y.; Parsons, L.H.; Ambasudhan, R.; Masliah, E.; Heinemann, S.F.; Piña-Crespo, J.C.; Lipton, S.A. Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss. Proc. Natl. Acad. Sci. USA, 2013, 110(27), E2518-E2527.
[http://dx.doi.org/10.1073/pnas.1306832110] [PMID: 23776240]
[26]
Sinnen, B.L.; Bowen, A.B.; Gibson, E.S.; Kennedy, M.J. Local and use-dependent effects of β-Amyloid oligomers on NMDA receptor function revealed by optical quantal analysis. J. Neurosci., 2016, 36(45), 11532-11543.
[http://dx.doi.org/10.1523/JNEUROSCI.1603-16.2016] [PMID: 27911757]
[27]
Takahashi, R.H.; Capetillo-Zarate, E.; Lin, M.T.; Milner, T.A.; Gouras, G.K. Co-occurrence of Alzheimer’s disease ß-amyloid and τ pathologies at synapses. Neurobiol. Aging, 2010, 31(7), 1145-1152.
[http://dx.doi.org/10.1016/j.neurobiolaging.2008.07.021] [PMID: 18771816]
[28]
Chabrier, M.A.; Cheng, D.; Castello, N.A.; Green, K.N.; LaFerla, F.M. Synergistic effects of amyloid-beta and wild-type human tau on dendritic spine loss in a floxed double transgenic model of Alzheimer’s disease. Neurobiol. Dis., 2014, 64, 107-117.
[http://dx.doi.org/10.1016/j.nbd.2014.01.007] [PMID: 24440055]
[29]
Castillo-Carranza, D.L.; Guerrero-Muñoz, M.J.; Sengupta, U.; Hernandez, C.; Barrett, A.D.; Dineley, K.; Kayed, R. Tau immunotherapy modulates both pathological tau and upstream amyloid pathology in an Alzheimer’s disease mouse model. J. Neurosci., 2015, 35(12), 4857-4868.
[http://dx.doi.org/10.1523/JNEUROSCI.4989-14.2015] [PMID: 25810517]
[30]
Morroni, F.; Sita, G.; Tarozzi, A.; Rimondini, R.; Hrelia, P. Early effects of Aβ1-42 oligomers injection in mice: Involvement of PI3K/Akt/GSK3 and MAPK/ERK1/2 pathways. Behav. Brain Res., 2016, 314, 106-115.
[http://dx.doi.org/10.1016/j.bbr.2016.08.002] [PMID: 27498145]
[31]
Haas, L.T.; Salazar, S.V.; Kostylev, M.A.; Um, J.W.; Kaufman, A.C.; Strittmatter, S.M. Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer’s disease. Brain, 2016, 139(Pt 2), 526-546.
[http://dx.doi.org/10.1093/brain/awv356] [PMID: 26667279]
[32]
Ding, Y.; Zhao, J.; Zhang, X.; Wang, S.; Viola, K.L.; Chow, F.E.; Zhang, Y.; Lippa, C.; Klein, W.L.; Gong, Y. Amyloid beta oligomers target to extracellular and intracellular neuronal synaptic proteins in Alzheimer’s disease. Front. Neurol., 2019, 10, 1140.
[http://dx.doi.org/10.3389/fneur.2019.01140] [PMID: 31736856]
[33]
Bomfim, T.R.; Forny-Germano, L.; Sathler, L.B.; Brito-Moreira, J.; Houzel, J.C.; Decker, H.; Silverman, M.A.; Kazi, H.; Melo, H.M.; McClean, P.L.; Holscher, C.; Arnold, S.E.; Talbot, K.; Klein, W.L.; Munoz, D.P.; Ferreira, S.T.; De Felice, F.G. An anti- diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer’s disease- associated Aβ oligomers. J. Clin. Invest., 2012, 122(4), 1339-1353.
[http://dx.doi.org/10.1172/JCI57256] [PMID: 22476196]
[34]
Pitt, J.; Wilcox, K.C.; Tortelli, V.; Diniz, L.P.; Oliveira, M.S.; Dobbins, C.; Yu, X.W.; Nandamuri, S.; Gomes, F.C.A.; DiNunno, N.; Viola, K.L.; De Felice, F.G.; Ferreira, S.T.; Klein, W.L. Neuroprotective astrocyte-derived insulin/insulin-like growth factor 1 stimulates endocytic processing and extracellular release of neuron-bound Aβ oligomers. Mol. Biol. Cell, 2017, 28(20), 2623-2636.
[http://dx.doi.org/10.1091/mbc.e17-06-0416] [PMID: 28963439]
[35]
Bartl, J.; Meyer, A.; Brendler, S.; Riederer, P.; Grünblatt, E. Different effects of soluble and aggregated amyloid β42 on gene/protein expression and enzyme activity involved in insulin and APP pathways. J. Neural Transm (Vienna), 2013, 120, 113-20.
[36]
Swerdlow, R.H. Mitochondria and mitochondrial cascades in Alzheimer’s disease. J. Alzheimers Dis., 2018, 62(3), 1403-1416.
[http://dx.doi.org/10.3233/JAD-170585] [PMID: 29036828]
[37]
Mroczko, B.; Groblewska, M.; Litman-Zawadzka, A.; Kornhuber, J.; Lewczuk, P. Cellular receptors of amyloid β oligomers (AβOs) in Alzheimer’s disease. Int. J. Mol. Sci., 2018, 19(7), 19.
[http://dx.doi.org/10.3390/ijms19071884] [PMID: 29954063]
[38]
Wilcox, K.C.; Lacor, P.N.; Pitt, J.; Klein, W.L. Aβ oligomer-induced synapse degeneration in Alzheimer’s disease. Cell. Mol. Neurobiol., 2011, 31(6), 939-948.
[http://dx.doi.org/10.1007/s10571-011-9691-4] [PMID: 21538118]
[39]
Krafft, G.A.; Klein, W.L. ADDLs and the signaling web that leads to Alzheimer’s disease. Neuropharmacology, 2010, 59(4-5), 230-242.
[http://dx.doi.org/10.1016/j.neuropharm.2010.07.012] [PMID: 20650286]
[40]
Kostylev, M.A.; Kaufman, A.C.; Nygaard, H.B.; Patel, P.; Haas, L.T.; Gunther, E.C.; Vortmeyer, A.; Strittmatter, S.M. Prion-protein-interacting amyloid-β oligomers of high molecular weight are tightly correlated with memory impairment in multiple alzheimer mouse models. J. Biol. Chem., 2015, 290(28), 17415-17438.
[http://dx.doi.org/10.1074/jbc.M115.643577] [PMID: 26018073]
[41]
Lesné, S.E.; Sherman, M.A.; Grant, M.; Kuskowski, M.; Schneider, J.A.; Bennett, D.A.; Ashe, K.H. Brain amyloid-β oligomers in ageing and Alzheimer’s disease. Brain, 2013, 136(Pt 5), 1383-1398.
[http://dx.doi.org/10.1093/brain/awt062] [PMID: 23576130]
[42]
Hussain, I.; Powell, D.; Howlett, D.R.; Tew, D.G.; Meek, T.D.; Chapman, C.; Gloger, I.S.; Murphy, K.E.; Southan, C.D.; Ryan, D.M.; Smith, T.S.; Simmons, D.L.; Walsh, F.S.; Dingwall, C.; Christie, G. Identification of a novel aspartic protease (Asp 2) as β-secretase. Mol. Cell. Neurosci., 1999, 14(6), 419-427.
[http://dx.doi.org/10.1006/mcne.1999.0811] [PMID: 10656250]
[43]
Hampel, H.; Vassar, R.; De Strooper, B.; Hardy, J.; Willem, M.; Singh, N.; Zhou, J.; Yan, R.; Vanmechelen, E.; De Vos, A.; Nisticò, R.; Corbo, M.; Imbimbo, B.P.; Streffer, J.; Voytyuk, I.; Timmers, M.; Tahami, M.A.A.; Irizarry, M.; Albala, B.; Koyama, A.; Watanabe, N.; Kimura, T.; Yarenis, L.; Lista, S.; Kramer, L.; Vergallo, A. The β-Secretase BACE1 in Alzheimer’s Disease. Biol. Psychiatry, 2021, 89(8), 745-756, S0006-3223(20)30063-9.
[PMID: 32223911]
[44]
Meakin, P.J.; Mezzapesa, A.; Benabou, E.; Haas, M.E.; Bonardo, B.; Grino, M.; Brunel, J.M.; Desbois-Mouthon, C.; Biddinger, S.B.; Govers, R.; Ashford, M.L.J.; Peiretti, F. The beta secretase BACE1 regulates the expression of insulin receptor in the liver. Nat. Commun., 2018, 9(1), 1306.
[http://dx.doi.org/10.1038/s41467-018-03755-2] [PMID: 29610518]
[45]
Das, B.; Yan, R. Role of BACE1 in Alzheimer’s synaptic function. Transl. Neurodegener., 2017, 6, 23.
[http://dx.doi.org/10.1186/s40035-017-0093-5] [PMID: 28855981]
[46]
Sun, X.; Bromley-Brits, K.; Song, W. Regulation of β-site APP- cleaving enzyme 1 gene expression and its role in Alzheimer’s disease. J. Neurochem., 2012, 120(Suppl. 1), 62-70.
[http://dx.doi.org/10.1111/j.1471-4159.2011.07515.x] [PMID: 22122349]
[47]
Wilkins, H.M.; Swerdlow, R.H. Amyloid precursor protein processing and bioenergetics. Brain Res. Bull., 2017, 133, 71-79. S0361923016302040.
[PMID: 27545490]
[48]
Wilkins, H.M.; Swerdlow, R.H. Amyloid precursor protein processing and bioenergetics. Brain Res. Bull., 2017, 133, 71-79.
[http://dx.doi.org/10.1016/j.brainresbull.2016.08.009] [PMID: 27545490]
[49]
Maho; Morishima-Kawashima. Molecular mechanism of the intramembrane cleavage of the β-carboxyl terminal fragment of amyloid precursor protein by γ-secretase. Front. Physiol., 2014, 5, 463.
[50]
Chasseigneaux, S.; Allinquant, B. Functions of Aβ, sAPPα and sAPPβ : similarities and differences. J. Neurochem., 2012, 120(Suppl. 1), 99-108.
[http://dx.doi.org/10.1111/j.1471-4159.2011.07584.x] [PMID: 22150401]
[51]
De Strooper, B.; Vassar, R.; Golde, T. The secretases: enzymes with therapeutic potential in Alzheimer disease. Nat. Rev. Neurol., 2010, 6(2), 99-107.
[http://dx.doi.org/10.1038/nrneurol.2009.218] [PMID: 20139999]
[52]
Willem, M.; Garratt, A.N.; Novak, B.; Citron, M.; Kaufmann, S.; Rittger, A.; DeStrooper, B.; Saftig, P.; Birchmeier, C.; Haass, C. Control of peripheral nerve myelination by the beta-secretase BACE1. Science, 2006, 314(5799), 664-666.
[http://dx.doi.org/10.1126/science.1132341] [PMID: 16990514]
[53]
Hu, X.; Hicks, C.W.; He, W.; Wong, P.; Macklin, W.B.; Trapp, B.D.; Yan, R. Bace1 modulates myelination in the central and peripheral nervous system. Nat. Neurosci., 2006, 9(12), 1520-1525.
[http://dx.doi.org/10.1038/nn1797] [PMID: 17099708]
[54]
Laird, F.M.; Cai, H.; Savonenko, A.V.; Farah, M.H.; He, K.; Melnikova, T.; Wen, H.; Chiang, H.C.; Xu, G.; Koliatsos, V.E.; Borchelt, D.R.; Price, D.L.; Lee, H.K.; Wong, P.C. BACE1, a major determinant of selective vulnerability of the brain to amyloid- beta amyloidogenesis, is essential for cognitive, emotional, and synaptic functions. J. Neurosci., 2005, 25(50), 11693-11709.
[http://dx.doi.org/10.1523/JNEUROSCI.2766-05.2005] [PMID: 16354928]
[55]
McConlogue, L.; Buttini, M.; Anderson, J.P.; Brigham, E.F.; Chen, K.S.; Freedman, S.B.; Games, D.; Johnson-Wood, K.; Lee, M.; Zeller, M.; Liu, W.; Motter, R.; Sinha, S. Partial reduction of BACE1 has dramatic effects on Alzheimer plaque and synaptic pathology in APP Transgenic Mice. J. Biol. Chem., 2007, 282(36), 26326-26334.
[http://dx.doi.org/10.1074/jbc.M611687200] [PMID: 17616527]
[56]
Sadleir, K.R.; Eimer, W.A.; Cole, S.L.; Vassar, R. Aβ reduction in BACE1 heterozygous null 5XFAD mice is associated with transgenic APP level. Mol. Neurodegener., 2015, 10, 1-16.
[http://dx.doi.org/10.1186/1750-1326-10-1] [PMID: 25567526]
[57]
Golde, T.E.; Petrucelli, L.; Lewis, J. Targeting Abeta and tau in Alzheimer’s disease, an early interim report. Exp. Neurol., 2010, 223(2), 252-266.
[http://dx.doi.org/10.1016/j.expneurol.2009.07.035] [PMID: 19716367]
[58]
Maloney, J.A.; Bainbridge, T.; Gustafson, A.; Zhang, S.; Kyauk, R.; Steiner, P.; van der Brug, M.; Liu, Y.; Ernst, J.A.; Watts, R.J.; Atwal, J.K. Molecular mechanisms of Alzheimer disease protection by the A673T allele of amyloid precursor protein. J. Biol. Chem., 2014, 289(45), 30990-31000.
[http://dx.doi.org/10.1074/jbc.M114.589069] [PMID: 25253696]
[59]
Jonsson, T.; Atwal, J.K.; Steinberg, S.; Snaedal, J.; Jonsson, P.V.; Bjornsson, S.; Stefansson, H.; Sulem, P.; Gudbjartsson, D.; Maloney, J.; Hoyte, K.; Gustafson, A.; Liu, Y.; Lu, Y.; Bhangale, T.; Graham, R.R.; Huttenlocher, J.; Bjornsdottir, G.; Andreassen, O.A.; Jönsson, E.G.; Palotie, A.; Behrens, T.W.; Magnusson, O.T.; Kong, A.; Thorsteinsdottir, U.; Watts, R.J.; Stefansson, K. A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline. Nature, 2012, 488(7409), 96-99.
[http://dx.doi.org/10.1038/nature11283] [PMID: 22801501]
[60]
Kennedy, M. E.; Stamford, A. W.; Chen, X.; Cox, K.; Cumming, J. N.; Dockendorf, M. F.; Egan, M.; Ereshefsky, L.; Hodgson, R. A.; Hyde, L. A. The BACE1 inhibitor verubecestat (MK-8931) reduces CNS ?-amyloid in animal models and in Alzheimers disease patients. Sci. Transl. Med., 2016, 8, 363ra150-363ra150.
[61]
Cebers, G.; Alexander, R.C.; Haeberlein, S.B.; Han, D.; Goldwater, R.; Ereshefsky, L.; Olsson, T.; Ye, N.; Rosen, L.; Russell, M. AZD3293: pharmacokinetic and pharmacodynamic effects in healthy subjects and patients with Alzheimer’s disease. J. Alzheimers Dis., 2017, 55(3), 1039-1053.
[http://dx.doi.org/10.3233/JAD-160701] [PMID: 27767991]
[62]
Kei, S.; Shunji, M.; Kyoko, M.; Tatsuya, Y.; Naoki, U.. BACE1 inhibitor lanabecestat (AZD3293) in a phase 1 study of healthy Japanese subjects: pharmacokinetics and effects on plasma and cerebrospinal fluid Aβ peptides. J. Clin. Pharmacol., 2017, 57(11), 1460-1471.
[63]
Kumar, D.; Ganeshpurkar, A.; Dileep, M.; Gyan, G.; Sanjeev, K.. Secretase inhibitors for the treatment of Alzheimer’s disease: Long road ahead. Eur. J. Med. Chem., 2018, 148, 436-452.
[64]
Ufer, M.; Rouzade-Dominguez, M.L.; Huledal, G.; Pezous, N.; Avrameas, A.; David, O.; Kretz, S.; Kucher, K.; Neumann, U.; Cha, J.H. Results From A First-In-Human Study With The BACE inhibitor CNP520. Alzheimers Dement., 2016, 200.
[http://dx.doi.org/10.1016/j.jalz.2016.06.351]
[65]
Tamagno, E.; Guglielmotto, M.; Monteleone, D.; Vercelli, A.; Tabaton, M. Transcriptional and post-transcriptional regulation of β-secretase. IUBMB Life, 2012, 64(12), 943-950.
[http://dx.doi.org/10.1002/iub.1099] [PMID: 23180460]
[66]
Haniu, M.; Denis, P.; Young, Y.; Mendiaz, E.A.; Fuller, J.; Hui, J.O.; Bennett, B.D.; Kahn, S.; Ross, S.; Burgess, T.; Katta, V.; Rogers, G.; Vassar, R.; Citron, M. Characterization of Alzheimer’s beta -secretase protein BACE. A pepsin family member with unusual properties. J. Biol. Chem., 2000, 275(28), 21099-21106.
[http://dx.doi.org/10.1074/jbc.M002095200] [PMID: 10887202]
[67]
Bhattacharyya, R.; Barren, C.; Kovacs, D.M. Palmitoylation of amyloid precursor protein regulates amyloidogenic processing in lipid rafts. J. Neurosci., 2013, 33(27), 11169-11183.
[http://dx.doi.org/10.1523/JNEUROSCI.4704-12.2013] [PMID: 23825420]
[68]
Kang, E.L.; Biscaro, B.; Piazza, F.; Tesco, G. BACE1 protein endocytosis and trafficking are differentially regulated by ubiquitination at lysine 501 and the Di-leucine motif in the carboxyl terminus. J. Biol. Chem., 2012, 287(51), 42867-42880.
[http://dx.doi.org/10.1074/jbc.M112.407072] [PMID: 23109336]
[69]
Wang, R.; Ying, Z.; Zhao, J.; Zhang, Y.; Wang, R.; Lu, H.; Deng, Y.; Song, W.; Qing, H. Lys(203) and Lys(382) are essential for the proteasomal degradation of BACE1. Curr. Alzheimer Res., 2012, 9(5), 606-615.
[http://dx.doi.org/10.2174/156720512800618026] [PMID: 22299711]
[70]
Ding, Y.; Ko, M.H.; Pehar, M.; Kotch, F.; Peters, N.R.; Luo, Y.; Salamat, S.M.; Puglielli, L. Biochemical inhibition of the acetyltransferases ATase1 and ATase2 reduces β-secretase (BACE1) levels and Aβ generation. J. Biol. Chem., 2012, 287(11), 8424-8433.
[http://dx.doi.org/10.1074/jbc.M111.310136] [PMID: 22267734]
[71]
Ko, M.H.; Puglielli, L. Two endoplasmic reticulum (ER)/ER Golgi intermediate compartment-based lysine acetyltransferases post- translationally regulate BACE1 levels. J. Biol. Chem., 2009, 284(4), 2482-2492.
[http://dx.doi.org/10.1074/jbc.M804901200] [PMID: 19011241]
[72]
Costantini, C.; Ko, M.H.; Jonas, M.C.; Puglielli, L. A reversible form of lysine acetylation in the ER and Golgi lumen controls the molecular stabilization of BACE1. Biochem. J., 2007, 407(3), 383-395.
[http://dx.doi.org/10.1042/BJ20070040] [PMID: 17425515]
[73]
Jonas, M.C.; Pehar, M.; Puglielli, L. AT-1 is the ER membrane acetyl-CoA transporter and is essential for cell viability. J. Cell Sci., 2010, 123(Pt 19), 3378-3388.
[http://dx.doi.org/10.1242/jcs.068841] [PMID: 20826464]
[74]
Bhat, A.H.; Maity, S.; Giri, K.; Ambatipudi, K. Protein glycosylation: Sweet or bitter for bacterial pathogens? Crit. Rev. Microbiol., 2019, 45(1), 82-102.
[http://dx.doi.org/10.1080/1040841X.2018.1547681] [PMID: 30632429]
[75]
Capell, A.; Steiner, H.; Willem, M.; Kaiser, H.; Meyer, C.; Walter, J.; Lammich, S.; Multhaup, G.; Haass, C. Maturation and pro-peptide cleavage of beta-secretase. J. Biol. Chem., 2000, 275(40), 30849-30854.
[http://dx.doi.org/10.1074/jbc.M003202200] [PMID: 10801872]
[76]
Huse, J.T.; Pijak, D.S.; Leslie, G.J.; Lee, V.M.; Doms, R.W. Maturation and endosomal targeting of beta-site amyloid precursor protein-cleaving enzyme. The Alzheimer’s disease beta-secretase. J. Biol. Chem., 2000, 275(43), 33729-33737.
[http://dx.doi.org/10.1074/jbc.M004175200] [PMID: 10924510]
[77]
Charlwood, J.; Dingwall, C.; Matico, R.; Hussain, I.; Johanson, K.; Moore, S.; Powell, D.J.; Skehel, J.M.; Ratcliffe, S.; Clarke, B.; Trill, J.; Sweitzer, S.; Camilleri, P. Characterization of the glycosylation profiles of Alzheimer’s beta -secretase protein Asp-2 expressed in a variety of cell lines. J. Biol. Chem., 2001, 276(20), 16739-16748.
[http://dx.doi.org/10.1074/jbc.M009361200] [PMID: 11278492]
[78]
Kizuka, Y.; Kitazume, S.; Fujinawa, R.; Saito, T.; Iwata, N.; Saido, T.C.; Nakano, M.; Yamaguchi, Y.; Hashimoto, Y.; Staufenbiel, M.; Hatsuta, H.; Murayama, S.; Manya, H.; Endo, T.; Taniguchi, N. An aberrant sugar modification of BACE1 blocks its lysosomal targeting in Alzheimer’s disease. EMBO Mol. Med., 2015, 7(2), 175-189.
[http://dx.doi.org/10.15252/emmm.201404438] [PMID: 25592972]
[79]
Fischer, F.; Molinari, M.; Bodendorf, U.; Paganetti, P. The disulphide bonds in the catalytic domain of BACE are critical but not essential for amyloid precursor protein processing activity. J. Neurochem., 2002, 80(6), 1079-1088.
[http://dx.doi.org/10.1046/j.0022-3042.2002.00806.x] [PMID: 11953458]
[80]
Sidera, C.; Parsons, R.; Austen, B. Post-translational processing of beta-secretase in Alzheimer’s disease. Proteomics, 2005, 5(6), 1533-1543.
[http://dx.doi.org/10.1002/pmic.200401185] [PMID: 15789346]
[81]
Kizuka, Y.; Nakano, M.; Kitazume, S.; Saito, T.; Saido, T.C.; Taniguchi, N. Bisecting GlcNAc modification stabilizes BACE1 protein under oxidative stress conditions. Biochem. J., 2016, 473(1), 21-30.
[http://dx.doi.org/10.1042/BJ20150607] [PMID: 26467158]
[82]
Taniguchi, N.; Takahashi, M.; Kizuka, Y.; Kitazume, S.; Shuvaev, V.V.; Ookawara, T.; Furuta, A. Glycation vs. glycosylation: a tale of two different chemistries and biology in Alzheimer’s disease. Glycoconj. J., 2016, 33(4), 487-497.
[http://dx.doi.org/10.1007/s10719-016-9690-2] [PMID: 27325408]
[83]
Kaur, I.; Yarov-Yarovoy, V.; Kirk, L.M.; Plambeck, K.E.; Barragan, E.V.; Ontiveros, E.S.; Díaz, E. Activity-dependent palmitoylation controls SynDIG1 stability, localization, and function. J. Neurosci., 2016, 36(29), 7562-7568.
[http://dx.doi.org/10.1523/JNEUROSCI.4859-14.2016] [PMID: 27445135]
[84]
Zhang, M.M.; Hang, H.C. Protein S-palmitoylation in cellular differentiation. Biochem. Soc. Trans., 2017, 45(1), 275-285.
[http://dx.doi.org/10.1042/BST20160236] [PMID: 28202682]
[85]
Andrew, R.J.; Fernandez, C.G.; Stanley, M.; Jiang, H.; Nguyen, P.; Rice, R.C.; Buggia-Prévot, V.; De Rossi, P.; Vetrivel, K.S.; Lamb, R.; Argemi, A.; Allaert, E.S.; Rathbun, E.M.; Krause, S.V.; Wagner, S.L.; Parent, A.T.; Holtzman, D.M.; Thinakaran, G. Lack of BACE1 S-palmitoylation reduces amyloid burden and mitigates memory deficits in transgenic mouse models of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA, 2017, 114(45), E9665-E9674.
[http://dx.doi.org/10.1073/pnas.1708568114] [PMID: 29078331]
[86]
Kazumi; Motoki; Hideaki; Kume; Akiko; Oda; Akira; Tamaoka; Ai; Hosaka. Neuronal β-amyloid generation is independent of lipid raft association of β-secretase BACE1: analysis with a palmitoylation-deficient mutant. Brain Behav., 2012.
[87]
Fabiani, C.; Antollini, S.S. Alzheimer’s disease as a membrane disorder: spatial cross-talk among beta-amyloid peptides, nicotinic acetylcholine receptors and lipid rafts. Front. Cell. Neurosci., 2019, 13, 309.
[http://dx.doi.org/10.3389/fncel.2019.00309] [PMID: 31379503]
[88]
Levental, I.; Grzybek, M.; Simons, K. Greasing their way: lipid modifications determine protein association with membrane rafts. Biochemistry, 2010, 49(30), 6305-6316.
[http://dx.doi.org/10.1021/bi100882y] [PMID: 20583817]
[89]
Hicks, D.A.; Nalivaeva, N.N.; Turner, A.J. Lipid rafts and Alzheimer’s disease: protein-lipid interactions and perturbation of signaling. Front. Physiol., 2012, 3, 189.
[http://dx.doi.org/10.3389/fphys.2012.00189] [PMID: 22737128]
[90]
Vetrivel, K.S.; Thinakaran, G. Membrane rafts in Alzheimer’s disease beta-amyloid production. Biochim. Biophys. Acta, 2010, 1801(8), 860-867.
[http://dx.doi.org/10.1016/j.bbalip.2010.03.007] [PMID: 20303415]
[91]
Marin, R.; Fabelo, N.; Martín, V.; Garcia-Esparcia, P.; Ferrer, I.; Quinto-Alemany, D.; Díaz, M. Anomalies occurring in lipid profiles and protein distribution in frontal cortex lipid rafts in dementia with Lewy bodies disclose neurochemical traits partially shared by Alzheimer’s and Parkinson’s diseases. Neurobiol. Aging, 2017, 49, 52-59.
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.08.027] [PMID: 27768960]
[92]
Benjannet, S.; Elagoz, A.; Wickham, L.; Mamarbachi, M.; Munzer, J.S.; Basak, A.; Lazure, C.; Cromlish, J.A.; Sisodia, S.; Checler, F.; Chrétien, M.; Seidah, N.G. Post-translational processing of beta-secretase (beta-amyloid-converting enzyme) and its ectodomain shedding. The pro- and transmembrane/cytosolic domains affect its cellular activity and amyloid-beta production. J. Biol. Chem., 2001, 276(14), 10879-10887.
[http://dx.doi.org/10.1074/jbc.M009899200] [PMID: 11152688]
[93]
Vassar, R.; Kuhn, P.H.; Haass, C.; Kennedy, M.E.; Rajendran, L.; Wong, P.C.; Lichtenthaler, S.F. Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects. J. Neurochem., 2014, 130(1), 4-28.
[http://dx.doi.org/10.1111/jnc.12715] [PMID: 24646365]
[94]
Ardito, F.; Giuliani, M.; Perrone, D.; Troiano, G.; Lo Muzio, L. The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review). Int. J. Mol. Med., 2017, 40(2), 271-280.
[http://dx.doi.org/10.3892/ijmm.2017.3036] [PMID: 28656226]
[95]
Hu, Y.B.; Dammer, E.B.; Ren, R.J.; Wang, G. The endosomal-lysosomal system: from acidification and cargo sorting to neurodegeneration. Transl. Neurodegener., 2015, 4, 18.
[http://dx.doi.org/10.1186/s40035-015-0041-1] [PMID: 26448863]
[96]
Song, W.J.; Son, M.Y.; Lee, H.W.; Seo, H.; Kim, J.H.; Chung, S.H. Enhancement of BACE1 Activity by p25/Cdk5-Mediated Phosphorylation in Alzheimer’s Disease. PLoS One, 2015, 10(8), e0136950.
[http://dx.doi.org/10.1371/journal.pone.0136950] [PMID: 26317805]
[97]
Sun, M.; Zhang, H. Par3 and aPKC regulate BACE1 endosome- to-TGN trafficking through PACS1. Neurobiol. Aging, 2017, 60, 129-140.
[http://dx.doi.org/10.1016/j.neurobiolaging.2017.08.024] [PMID: 28946017]
[98]
Kosicek, M.; Wunderlich, P.; Walter, J.; Hecimovic, S. GGA1 overexpression attenuates amyloidogenic processing of the amyloid precursor protein in Niemann-Pick type C cells. Biochem. Biophys. Res. Commun., 2014, 450(1), 160-165.
[http://dx.doi.org/10.1016/j.bbrc.2014.05.083] [PMID: 24866237]
[99]
Mañucat-Tan, N.B.; Saadipour, K.; Wang, Y.J.; Bobrovskaya, L.; Zhou, X.F. Cellular trafficking of amyloid precursor protein in amyloidogenesis physiological and pathological significance. Mol. Neurobiol., 2019, 56(2), 812-830.
[http://dx.doi.org/10.1007/s12035-018-1106-9] [PMID: 29797184]
[100]
Chia, P.Z.; Toh, W.H.; Sharples, R.; Gasnereau, I.; Hill, A.F.; Gleeson, P.A. Intracellular itinerary of internalised β-secretase, BACE1, and its potential impact on β-amyloid peptide biogenesis. Traffic, 2013, 14(9), 997-1013.
[http://dx.doi.org/10.1111/tra.12088] [PMID: 23773724]
[101]
Tan, J.; Evin, G. Β-site APP-cleaving enzyme 1 trafficking and Alzheimer’s disease pathogenesis. J. Neurochem., 2012, 120(6), 869-880.
[http://dx.doi.org/10.1111/j.1471-4159.2011.07623.x] [PMID: 22171895]
[102]
Toh, W.H.; Chia, P.Z.C.; Hossain, M.I.; Gleeson, P.A. GGA1 regulates signal-dependent sorting of BACE1 to recycling endosomes, which moderates Aβ production. Mol. Biol. Cell, 2018, 29(2), 191-208.
[http://dx.doi.org/10.1091/mbc.E17-05-0270] [PMID: 29142073]
[103]
Quan, Q.; Qian, Y.; Li, X.; Li, M. Pioglitazone reduces β amyloid levels via inhibition of PPARγ phosphorylation in a neuronal model of Alzheimer’s disease. Front. Aging Neurosci., 2019, 11, 178.
[http://dx.doi.org/10.3389/fnagi.2019.00178] [PMID: 31379559]
[104]
Blasiak, J.; Pawlowska, E.; Szczepanska, J.; Kaarniranta, K. Interplay between Autophagy and the Ubiquitin-Proteasome System and Its Role in the Pathogenesis of Age-Related Macular Degeneration. Int. J. Mol. Sci., 2019, 20(1), 20.
[http://dx.doi.org/10.3390/ijms20010210] [PMID: 30626110]
[105]
Puertollano, R.; Bonifacino, J.S. Interactions of GGA3 with the ubiquitin sorting machinery. Nat. Cell Biol., 2004, 6(3), 244-251.
[http://dx.doi.org/10.1038/ncb1106] [PMID: 15039775]
[106]
Yeates, E.F.; Tesco, G. The endosome-associated deubiquitinating enzyme USP8 regulates BACE1 enzyme ubiquitination and degradation. J. Biol. Chem., 2016, 291(30), 15753-15766.
[http://dx.doi.org/10.1074/jbc.M116.718023] [PMID: 27302062]
[107]
Hoppe, J.B.; Salbego, C.G.; Cimarosti, H. SUMOylation: novel neuroprotective approach for Alzheimer’s disease? Aging Dis., 2015, 6(5), 322-330.
[http://dx.doi.org/10.14336/AD.2014.1205] [PMID: 26425387]
[108]
Nisticò, R.; Ferraina, C.; Marconi, V.; Blandini, F.; Negri, L.; Egebjerg, J.; Feligioni, M. Age-related changes of protein SUMOylation balance in the AβPP Tg2576 mouse model of Alzheimer’s disease. Front. Pharmacol., 2014, 5, 63.
[PMID: 24778618]
[109]
Qin, M.; Li, H.; Bao, J.; Xia, Y.; Ke, D.; Wang, Q.; Liu, R.; Wang, J.Z.; Zhang, B.; Shu, X.; Wang, X. SET SUMOylation promotes its cytoplasmic retention and induces tau pathology and cognitive impairments. Acta Neuropathol. Commun., 2019, 7(1), 21.
[http://dx.doi.org/10.1186/s40478-019-0663-0] [PMID: 30767764]
[110]
Bao, J.; Qin, M.; Mahaman, Y.A.R.; Zhang, B.; Huang, F.; Zeng, K.; Xia, Y.; Ke, D.; Wang, Q.; Liu, R.; Wang, J.Z.; Ye, K.; Wang, X. BACE1 SUMOylation increases its stability and escalates the protease activity in Alzheimer’s disease. Proc. Natl. Acad. Sci. USA, 2018, 115(15), 3954-3959.
[http://dx.doi.org/10.1073/pnas.1800498115] [PMID: 29581300]

Rights & Permissions Print Cite
Article Metrics
32
4
© 2024 Bentham Science Publishers | Privacy Policy