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Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Review Article

The Roles of Ciliary Neurotrophic Factor - from Neuronutrition to Energy Metabolism

Author(s): Huifang Guo, Peng Chen, Runfan Luo, Yuting Zhang, Xi Xu* and Xingchun Gou*

Volume 29, Issue 10, 2022

Published on: 27 September, 2022

Page: [815 - 828] Pages: 14

DOI: 10.2174/0929866529666220905105800

Price: $65

Abstract

Ciliary neurotrophic factor (CNTF) is a pluripotent neurotrophic factor originally isolated from chicken embryo ciliary neurons. It has a powerful role in developing and maintaining the optic nervous system and has been used for many vision-related diseases. It also plays an important role in the neurogenesis, regeneration and survival of other neurons, including neural stem cells, dorsal root ganglion, sensory neurons and motor neurons. CNTF is related to neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. In addition to its role in the nervous system, CNTF regulates the balance of energy metabolism and the administration of CNTF induces body weight loss. More CNTF functions have been found with the deepening of study, such as protecting and promoting cardiomyocyte proliferation. In addition, CNTF even participates in mental illness and inflammation suppressing. CNTF exerts multidirectional physiological activity by regulating the transcription of various genes through a variety of signalling pathways (including JAK/STAT, MAPK, and PI3K/AKT). This review summarizes the roles and mechanisms of CNTF in the optic nervous system, retinal-related diseases, neuronal protection, and especially nutrition, energy metabolism and other aspects.

Keywords: CNTF, neuronal protection, retinal-related diseases, nutrition, energy metabolism, neuronutrition.

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Graphical Abstract

[1]
Adler, R.; Landa, K.B.; Manthorpe, M.; Varon, S. Cholinergic neuronotrophic factors: Intraocular distribution of trophic activity for ciliary neurons. Science, 1979, 204(4400), 1434-1436.
[http://dx.doi.org/10.1126/science.451576] [PMID: 451576]
[2]
Krüttgen, A.; Grötzinger, J.; Kurapkat, G.; Weis, J.; Simon, R.; Thier, M.; Schröder, M.; Heinrich, P.; Wollmer, A.; Comeau, M.; Müllberg, J.; Rose-John, S. Human ciliary neurotrophic factor: A structure-function analysis. Biochem. J., 1995, 309(1), 215-220.
[http://dx.doi.org/10.1042/bj3090215] [PMID: 7619059]
[3]
Rose-John, S. Interleukin-6 family cytokines. Cold Spring Harb. Perspect. Biol., 2018, 10(2), a028415.
[http://dx.doi.org/10.1101/cshperspect.a028415] [PMID: 28620096]
[4]
Jones, S.A.; Jenkins, B.J. Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer. Nat. Rev. Immunol., 2018, 18(12), 773-789.
[http://dx.doi.org/10.1038/s41577-018-0066-7] [PMID: 30254251]
[5]
Murakami, M.; Kamimura, D.; Hirano, T. Pleiotropy and specificity: Insights from the interleukin 6 family of cytokines. Immunity, 2019, 50(4), 812-831.
[http://dx.doi.org/10.1016/j.immuni.2019.03.027] [PMID: 30995501]
[6]
Kang, S.S.; Keasey, M.P.; Cai, J.; Hagg, T. Loss of neuron-astroglial interaction rapidly induces protective CNTF expression after stroke in mice. J. Neurosci., 2012, 32(27), 9277-9287.
[http://dx.doi.org/10.1523/JNEUROSCI.1746-12.2012] [PMID: 22764235]
[7]
Keasey, M.P.; Kang, S.S.; Lovins, C.; Hagg, T. Inhibition of a novel specific neuroglial integrin signaling pathway increases STAT3-mediated CNTF expression. Cell Commun. Signal., 2013, 11(1), 35.
[http://dx.doi.org/10.1186/1478-811X-11-35] [PMID: 23693126]
[8]
Rudge, J.S.; Morrissey, D.; Lindsay, R.M.; Pasnikowski, E.M. Regulation of ciliary neurotrophic factor in cultured rat hippocampal astrocytes. Eur. J. Neurosci., 1994, 6(2), 218-229.
[http://dx.doi.org/10.1111/j.1460-9568.1994.tb00264.x] [PMID: 8167843]
[9]
Ola, M.S.; Ahmed, M.M.; Abuohashish, H.M.; Al-Rejaie, S.S.; Alhomida, A.S. Telmisartan ameliorates neurotrophic support and oxidative stress in the retina of streptozotocin-induced diabetic rats. Neurochem. Res., 2013, 38(8), 1572-1579.
[http://dx.doi.org/10.1007/s11064-013-1058-4] [PMID: 23624827]
[10]
Modi, K.K.; Sendtner, M.; Pahan, K. Up-regulation of ciliary neurotrophic factor in astrocytes by aspirin: Implications for remyelination in multiple sclerosis. J. Biol. Chem., 2013, 288(25), 18533-18545.
[http://dx.doi.org/10.1074/jbc.M112.447268] [PMID: 23653362]
[11]
Al-Ani, A.; Sunba, S.; Hafeez, B.; Toms, D.; Ungrin, M. in vitro maturation of retinal pigment epithelium is essential for maintaining high expression of key functional genes. Int. J. Mol. Sci., 2020, 21(17), 6066.
[http://dx.doi.org/10.3390/ijms21176066] [PMID: 32842471]
[12]
Zhou, W.D.; Wang, L.L.; Zhou, L.B.; Bin, W.; Bao, T.P.; Zhang, Y.; Shu, J.; Yang, W.X.; Hui, L.L.; Jin, R.; Zhuang, L.L.; Zhou, G.P. All-trans retinoic acid upregulates the expression of ciliary neurotrophic factor in retinal pigment epithelial cells. Cell Biochem. Funct., 2017, 35(4), 202-208.
[http://dx.doi.org/10.1002/cbf.3264] [PMID: 28589680]
[13]
Ma, M.; Zhao, S.; Zhang, J.; Sun, T.; Fan, Y.; Zheng, Z. High glucose-induced TRPC6 channel activation decreases glutamate uptake in rat retinal müller cells. Front. Pharmacol., 2020, 10, 1668.
[http://dx.doi.org/10.3389/fphar.2019.01668] [PMID: 32116675]
[14]
Davis, S.; Aldrich, T.H.; Stahl, N.; Pan, L.; Taga, T.; Kishimoto, T.; Ip, N.Y.; Yancopoulos, G.D. LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor. Science, 1993, 260(5115), 1805-1808.
[http://dx.doi.org/10.1126/science.8390097] [PMID: 8390097]
[15]
Lee, N.; Spearry, R.P.; Rydyznski, C.E.; MacLennan, A.J. Muscle ciliary neurotrophic factor receptor α contributes to motor neuron STAT3 activation following peripheral nerve lesion. Eur. J. Neurosci., 2019, 49(9), 1084-1090.
[PMID: 30554447]
[16]
Lee, N.; Wanek, H.A.; MacLennan, A.J. Muscle ciliary neurotrophic factor receptor α helps maintain choline acetyltransferase levels in denervated motor neurons following peripheral nerve lesion. Exp. Neurol., 2019, 317, 202-205.
[http://dx.doi.org/10.1016/j.expneurol.2019.03.009] [PMID: 30902524]
[17]
Liu, H.; Liu, G.; Bi, Y. CNTF regulates neurite outgrowth and neuronal migration through JAK2/STAT3 and PI3K/Akt signaling pathways of DRG explants with gp120-induced neurotoxicity in vitro. Neurosci. Lett., 2014, 569, 110-115.
[http://dx.doi.org/10.1016/j.neulet.2014.03.071] [PMID: 24708926]
[18]
Larsen, J.V.; Hansen, M.; Møller, B.; Madsen, P.; Scheller, J.; Nielsen, M.; Petersen, C.M. Sortilin facilitates signaling of ciliary neurotrophic factor and related helical type 1 cytokines targeting the gp130/leukemia inhibitory factor receptor beta heterodimer. Mol. Cell. Biol., 2010, 30(17), 4175-4187.
[http://dx.doi.org/10.1128/MCB.00274-10] [PMID: 20584990]
[19]
Dutt, K.; Cao, Y.; Ezeonu, I. Ciliary neurotrophic factor: A survival and differentiation inducer in human retinal progenitors. in vitro Cell. Dev. Biol. Anim., 2010, 46(7), 635-646.
[http://dx.doi.org/10.1007/s11626-010-9319-x] [PMID: 20428961]
[20]
Dulz, S.; Bassal, M.; Flachsbarth, K.; Riecken, K.; Fehse, B.; Schlichting, S.; Bartsch, S.; Bartsch, U. Intravitreal co-administration of GDNF and CNTF confers synergistic and long-lasting protection against injury-induced cell death of retinal ganglion cells in mice. Cells, 2020, 9(9), 2082.
[http://dx.doi.org/10.3390/cells9092082] [PMID: 32932933]
[21]
Joly, S.; Dalkara, D.; Pernet, V. Sphingosine 1-phosphate receptor 1 modulates CNTF-induced axonal growth and neuroprotection in the mouse visual system. Neural Plast., 2017, 2017, 6818970.
[http://dx.doi.org/10.1155/2017/6818970] [PMID: 29234527]
[22]
Heiduschka, P.; Renninger, D.; Fischer, D.; Müller, A.; Hofmeister, S.; Schraermeyer, U. Lens injury has a protective effect on photoreceptors in the RCS rat. ISRN Ophthalmol., 2013, 2013, 814814.
[http://dx.doi.org/10.1155/2013/814814] [PMID: 24558606]
[23]
Mathews, M.K.; Guo, Y.; Langenberg, P.; Bernstein, S.L. Ciliary neurotrophic factor (CNTF)-mediated ganglion cell survival in a rodent model of non-arteritic anterior ischaemic optic neuropathy (NAION). Br. J. Ophthalmol., 2015, 99(1), 133-137.
[http://dx.doi.org/10.1136/bjophthalmol-2014-305969] [PMID: 25336580]
[24]
Wang, W.J.; Jin, W.; Yang, A.H.; Chen, Z.; Xing, Y.Q. Protective effects of ciliary neurotrophic factor on the retinal ganglion cells by injure of hydrogen peroxide. Int. J. Ophthalmol., 2018, 11(6), 923-928.
[PMID: 29977802]
[25]
Ji, J.Z.; Elyaman, W.; Yip, H.K.; Lee, V.W.H.; Yick, L.W.; Hugon, J.; So, K.F. CNTF promotes survival of retinal ganglion cells after induction of ocular hypertension in rats: The possible involvement of STAT3 pathway. Eur. J. Neurosci., 2004, 19(2), 265-272.
[http://dx.doi.org/10.1111/j.0953-816X.2003.03107.x] [PMID: 14725620]
[26]
Yin, D-P.; Chen, Q-Y.; Liu, L. Synergetic effects of ciliary neurotrophic factor and olfactory ensheathing cells on optic nerve reparation (complete translation). Neural Regen. Res., 2016, 11, 1006-1012.
[27]
Leibinger, M.; Andreadaki, A.; Diekmann, H.; Fischer, D. Neuronal STAT3 activation is essential for CNTF- and inflammatory stimulation-induced CNS axon regeneration. Cell Death Dis., 2013, 4(9), e805-e805.
[http://dx.doi.org/10.1038/cddis.2013.310] [PMID: 24052073]
[28]
Hodgetts, S.I.; Harvey, A.R. Neurotrophic factors used to treat spinal cord injury. Vitam. Horm., 2017, 104, 405-457.
[29]
Hodgetts, S.I.; Yoon, J.H.; Fogliani, A.; Akinpelu, E.A.; Baron-Heeris, D.; Houwers, I.G.J.; Wheeler, L.P.G.; Majda, B.T.; Santhakumar, S.; Lovett, S.J.; Duce, E.; Pollett, M.A.; Wiseman, T.M.; Fehily, B.; Harvey, A.R. Cortical AAV-CNTF gene therapy combined with intraspinal mesenchymal precursor cell transplantation promotes functional and morphological outcomes after spinal cord injury in adult rats. Neural Plast., 2018, 2018, 9828725.
[http://dx.doi.org/10.1155/2018/9828725] [PMID: 30245710]
[30]
Müller, A.; Hauk, T.G.; Leibinger, M.; Marienfeld, R.; Fischer, D. Exogenous CNTF stimulates axon regeneration of retinal ganglion cells partially via endogenous CNTF. Mol. Cell. Neurosci., 2009, 41(2), 233-246.
[http://dx.doi.org/10.1016/j.mcn.2009.03.002] [PMID: 19332123]
[31]
LeVaillant, C.J.; Sharma, A.; Muhling, J.; Wheeler, L.P.G.; Cozens, G.S.; Hellström, M.; Rodger, J.; Harvey, A.R. Significant changes in endogenous retinal gene expression assessed 1 year after a single intraocular injection of AAV-CNTF or AAV-BDNF. Mol. Ther. Methods Clin. Dev., 2016, 3, 16078.
[http://dx.doi.org/10.1038/mtm.2016.78] [PMID: 27933306]
[32]
Flachsbarth, K.; Jankowiak, W.; Kruszewski, K.; Helbing, S.; Bartsch, S.; Bartsch, U. Pronounced synergistic neuroprotective effect of GDNF and CNTF on axotomized retinal ganglion cells in the adult mouse. Exp. Eye Res., 2018, 176, 258-265.
[http://dx.doi.org/10.1016/j.exer.2018.09.006] [PMID: 30237104]
[33]
Flachsbarth, K.; Kruszewski, K.; Jung, G.; Jankowiak, W.; Riecken, K.; Wagenfeld, L.; Richard, G.; Fehse, B.; Bartsch, U. Neural stem cell-based intraocular administration of ciliary neurotrophic factor attenuates the loss of axotomized ganglion cells in adult mice. Invest. Ophthalmol. Vis. Sci., 2014, 55(11), 7029-7039.
[http://dx.doi.org/10.1167/iovs.14-15266] [PMID: 25270193]
[34]
Cen, L.P.; Liang, J.J.; Chen, J.; Harvey, A.R.; Ng, T.K.; Zhang, M.; Pang, C.P.; Cui, Q.; Fan, Y.M. AAV-mediated transfer of RhoA shRNA and CNTF promotes retinal ganglion cell survival and axon regeneration. Neuroscience, 2017, 343, 472-482.
[http://dx.doi.org/10.1016/j.neuroscience.2016.12.027] [PMID: 28017835]
[35]
Yungher, B.J.; Ribeiro, M.; Park, K.K. Regenerative responses and axon pathfinding of retinal ganglion cells in chronically injured mice. Invest. Ophthalmol. Vis. Sci., 2017, 58(3), 1743-1750.
[http://dx.doi.org/10.1167/iovs.16-19873] [PMID: 28324115]
[36]
Hellström, M.; Pollett, M.A.; Harvey, A.R. Post-injury delivery of rAAV2-CNTF combined with short-term pharmacotherapy is neuroprotective and promotes extensive axonal regeneration after optic nerve trauma. J. Neurotrauma, 2011, 28(12), 2475-2483.
[http://dx.doi.org/10.1089/neu.2011.1928] [PMID: 21861632]
[37]
Johnson, T.V.; Bull, N.D.; Martin, K.R. Neurotrophic factor delivery as a protective treatment for glaucoma. Exp. Eye Res., 2011, 93(2), 196-203.
[http://dx.doi.org/10.1016/j.exer.2010.05.016] [PMID: 20685205]
[38]
Ma, M.; Xu, Y.; Xiong, S.; Zhang, J.; Gu, Q.; Ke, B.; Xu, X. Involvement of ciliary neurotrophic factor in early diabetic retinal neuropathy in streptozotocin-induced diabetic rats. Eye (Lond.), 2018, 32(9), 1463-1471.
[http://dx.doi.org/10.1038/s41433-018-0110-7] [PMID: 29795129]
[39]
Cui, Y.; Xu, N.; Xu, W.; Xu, G. Mesenchymal stem cells attenuate hydrogen peroxide-induced oxidative stress and enhance neuroprotective effects in retinal ganglion cells in vitro. Cell. Dev. Biol. Anim., 2017, 53(4), 328-335.
[http://dx.doi.org/10.1007/s11626-016-0115-0] [PMID: 27864663]
[40]
Schultz, R.; Krug, M.; Precht, M.; Wohl, S.G.; Witte, O.W.; Schmeer, C. Frataxin overexpression in Müller cells protects retinal ganglion cells in a mouse model of ischemia/reperfusion injury in vivo. Sci. Rep., 2018, 8(1), 4846.
[http://dx.doi.org/10.1038/s41598-018-22887-5] [PMID: 29555919]
[41]
Enayati, S.; Chang, K.; Achour, H.; Cho, K.S.; Xu, F.; Guo, S.Z.; Enayati, K.; Xie, J.; Zhao, E.; Turunen, T.; Sehic, A.; Lu, L.; Utheim, T.P.; Chen, D.F. Electrical stimulation induces retinal müller cell proliferation and their progenitor cell potential. Cells, 2020, 9(3), 9.
[http://dx.doi.org/10.3390/cells9030781] [PMID: 32210151]
[42]
Yuan, R.; Yang, M.; Fan, W.; Lan, J.; Zhou, Y.G. Paired immunoglobulin-like receptor b inhibition in müller cells promotes neurite regeneration after retinal ganglion cell injury in vitro. Neurosci. Bull., 2020, 36(9), 972-984.
[http://dx.doi.org/10.1007/s12264-020-00510-w] [PMID: 32445021]
[43]
Vigneswara, V.; Akpan, N.; Berry, M.; Logan, A.; Troy, C.M.; Ahmed, Z. Combined suppression of CASP2 and CASP6 protects retinal ganglion cells from apoptosis and promotes axon regeneration through CNTF-mediated JAK/STAT signalling. Brain, 2014, 137(6), 1656-1675.
[http://dx.doi.org/10.1093/brain/awu037] [PMID: 24727569]
[44]
Joly, S.; Pernet, V.; Chemtob, S.; Di Polo, A.; Lachapelle, P. Neuroprotection in the juvenile rat model of light-induced retinopathy: Evidence suggesting a role for FGF-2 and CNTF. Invest. Ophthalmol. Vis. Sci., 2007, 48(5), 2311-2320.
[http://dx.doi.org/10.1167/iovs.06-1205] [PMID: 17460296]
[45]
Li, S.; Sato, K.; Gordon, W.C.; Sendtner, M.; Bazan, N.G.; Jin, M. Ciliary neurotrophic factor (CNTF) protects retinal cone and rod photoreceptors by suppressing excessive formation of the visual pigments. J. Biol. Chem., 2018, 293(39), 15256-15268.
[http://dx.doi.org/10.1074/jbc.RA118.004008] [PMID: 30115683]
[46]
Valiente-Soriano, F.J.; Ortín-Martínez, A.; Di Pierdomenico, J.; García-Ayuso, D.; Gallego-Ortega, A.; Miralles de Imperial-Ollero, J.A.; Jiménez-López, M.; Villegas-Pérez, M.P.; Wheeler, L.A.; Vidal-Sanz, M. Topical brimonidine or intravitreal BDNF, CNTF, or bFGF protect cones against phototoxicity. Transl. Vis. Sci. Technol., 2019, 8(6), 36.
[http://dx.doi.org/10.1167/tvst.8.6.36] [PMID: 31890348]
[47]
Aslam, S.A.; Davies, W.I.L.; Singh, M.S.; Charbel Issa, P.; Barnard, A.R.; Scott, R.A.H.; MacLaren, R.E. Cone photoreceptor neuroprotection conferred by CNTF in a novel in vivo model of battlefield retinal laser injury. Invest. Ophthalmol. Vis. Sci., 2013, 54(8), 5456-5465.
[http://dx.doi.org/10.1167/iovs.13-11623] [PMID: 23744998]
[48]
Lipinski, D.M.; Barnard, A.R.; Singh, M.S.; Martin, C.; Lee, E.J.; Davies, W.I.L.; MacLaren, R.E. CNTF gene therapy confers lifelong neuroprotection in a mouse model of human retinitis pigmentosa. Mol. Ther., 2015, 23(8), 1308-1319.
[http://dx.doi.org/10.1038/mt.2015.68] [PMID: 25896245]
[49]
Rhee, K.D.; Nusinowitz, S.; Chao, K.; Yu, F.; Bok, D.; Yang, X.J. CNTF-mediated protection of photoreceptors requires initial activation of the cytokine receptor gp130 in Müller glial cells. Proc. Natl. Acad. Sci. USA, 2013, 110(47), E4520-E4529.
[http://dx.doi.org/10.1073/pnas.1303604110] [PMID: 24191003]
[50]
McGill, T.J.; Prusky, G.T.; Douglas, R.M.; Yasumura, D.; Matthes, M.T.; Nune, G.; Donohue-Rolfe, K.; Yang, H.; Niculescu, D.; Hauswirth, W.W.; Girman, S.V.; Lund, R.D.; Duncan, J.L.; LaVail, M.M. Intraocular CNTF reduces vision in normal rats in a dose-dependent manner. Invest. Ophthalmol. Vis. Sci., 2007, 48(12), 5756-5766.
[http://dx.doi.org/10.1167/iovs.07-0054] [PMID: 18055829]
[51]
Li, Y.; Tao, W.; Luo, L.; Huang, D.; Kauper, K.; Stabila, P.; LaVail, M.M.; Laties, A.M.; Wen, R. CNTF induces regeneration of cone outer segments in a rat model of retinal degeneration. PLoS One, 2010, 5(3), e9495.
[http://dx.doi.org/10.1371/journal.pone.0009495] [PMID: 20209167]
[52]
Wen, R.; Tao, W.; Luo, L.; Huang, D.; Kauper, K.; Stabila, P.; LaVail, M.M.; Laties, A.M.; Li, Y. Regeneration of cone outer segments induced by CNTF. Adv. Exp. Med. Biol., 2012, 723, 93-99.
[http://dx.doi.org/10.1007/978-1-4614-0631-0_13] [PMID: 22183320]
[53]
Kassen, S.C.; Thummel, R.; Campochiaro, L.A.; Harding, M.J.; Bennett, N.A.; Hyde, D.R. CNTF induces photoreceptor neuroprotection and Müller glial cell proliferation through two different signaling pathways in the adult zebrafish retina. Exp. Eye Res., 2009, 88(6), 1051-1064.
[http://dx.doi.org/10.1016/j.exer.2009.01.007] [PMID: 19450453]
[54]
Wang, Y.; Rhee, K.D.; Pellegrini, M.; Yang, X.J. Impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration. Sci. Rep., 2020, 10(1), 6593.
[http://dx.doi.org/10.1038/s41598-020-63519-1] [PMID: 32313077]
[55]
Talcott, K.E.; Ratnam, K.; Sundquist, S.M.; Lucero, A.S.; Lujan, B.J.; Tao, W.; Porco, T.C.; Roorda, A.; Duncan, J.L. Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic factor treatment. Invest. Ophthalmol. Vis. Sci., 2011, 52(5), 2219-2226.
[http://dx.doi.org/10.1167/iovs.10-6479] [PMID: 21087953]
[56]
Komáromy, A.M.; Rowlan, J.S.; Corr, A.T.P.; Reinstein, S.L.; Boye, S.L.; Cooper, A.E.; Gonzalez, A.; Levy, B.; Wen, R.; Hauswirth, W.W.; Beltran, W.A.; Aguirre, G.D. Transient photoreceptor deconstruction by CNTF enhances rAAV-mediated cone functional rescue in late stage CNGB3-achromatopsia. Mol. Ther., 2013, 21(6), 1131-1141.
[http://dx.doi.org/10.1038/mt.2013.50] [PMID: 23568263]
[57]
Marangoni, D.; Vijayasarathy, C.; Bush, R.A.; Wei, L.L.; Wen, R.; Sieving, P.A. Intravitreal ciliary neurotrophic factor transiently improves cone-mediated function in a CNGB3 −/− mouse model of achromatopsia. Invest. Ophthalmol. Vis. Sci., 2015, 56(11), 6810-6822.
[http://dx.doi.org/10.1167/iovs.15-16866] [PMID: 26567794]
[58]
Langlo, C.; Dubis, A.; Michaelides, M.; Carroll, J. CNGB3-achromatopsia clinical trial with CNTF: Diminished rod pathway responses with no evidence of improvement in cone function. Invest. Ophthalmol. Vis. Sci., 2015, 56(3), 1505-1505.
[http://dx.doi.org/10.1167/iovs.14-15897] [PMID: 25737149]
[59]
Li, R.; Wen, R.; Banzon, T.; Maminishkis, A.; Miller, S.S. CNTF mediates neurotrophic factor secretion and fluid absorption in human retinal pigment epithelium. PLoS One, 2011, 6(9), e23148.
[http://dx.doi.org/10.1371/journal.pone.0023148] [PMID: 21912637]
[60]
Lin, W.; Xu, G. Over-expression of CNTF in bone marrow mesenchymal stem cells protects RPE cells from short-wavelength, blue-light injury. In Vitro Cell. Dev. Biol. Anim., 2018, 54(5), 355-365.
[http://dx.doi.org/10.1007/s11626-018-0243-9] [PMID: 29564604]
[61]
Huang, Q.; Ding, Y.; Yu, J.; Li, J.; Xiang, Y.; Tao, N. Induction of differentiation of mesenchymal stem cells into retinal pigment epithelial cells for retinal regeneration by using ciliary neurotrophic factor in diabetic rats. Curr. Med. Sci., 2021, 41(1), 145-152.
[http://dx.doi.org/10.1007/s11596-021-2329-y] [PMID: 33582919]
[62]
Goureau, O.; Rhee, K.D.; Yang, X.J. Ciliary neurotrophic factor promotes muller glia differentiation from the postnatal retinal progenitor pool. Dev. Neurosci., 2004, 26(5-6), 359-370.
[http://dx.doi.org/10.1159/000082278] [PMID: 15855765]
[63]
Beach, K.M.; Wang, J.; Otteson, D.C. Regulation of stem cell properties of müller glia by jak/stat and mapk signaling in the mammalian retina. Stem Cells Int., 2017, 2017, 1-15.
[http://dx.doi.org/10.1155/2017/1610691] [PMID: 28194183]
[64]
Laughter, M.R.; Bardill, J.R.; Ammar, D.A.; Pena, B.; Calkins, D.J.; Park, D. Injectable neurotrophic factor delivery system supporting retinal ganglion cell survival and regeneration following optic nerve crush. ACS Biomater. Sci. Eng., 2018, 4(9), 3374-3383.
[http://dx.doi.org/10.1021/acsbiomaterials.8b00803] [PMID: 31431919]
[65]
Xie, L.; Yin, Y.; Benowitz, L. Chemokine CCL5 promotes robust optic nerve regeneration and mediates many of the effects of CNTF gene therapy. Proc. Natl. Acad. Sci. USA, 2021, 118(9), e2017282118.
[http://dx.doi.org/10.1073/pnas.2017282118] [PMID: 33627402]
[66]
Bucher, F.; Aguilar, E.; Marra, K.V.; Rapp, J.; Arnold, J.; Diaz-Aguilar, S.; Lange, C.; Agostini, H.; Schlunck, G.; Stahl, A.; Friedlander, M. CNTF prevents development of outer retinal neovascularization through upregulation of CxCl10. Invest. Ophthalmol. Vis. Sci., 2020, 61(10), 20.
[http://dx.doi.org/10.1167/iovs.61.10.20] [PMID: 32780864]
[67]
Todd, L.; Squires, N.; Suarez, L.; Fischer, A.J. Jak/Stat signaling regulates the proliferation and neurogenic potential of Müller glia-derived progenitor cells in the avian retina. Sci. Rep., 2016, 6(1), 35703.
[http://dx.doi.org/10.1038/srep35703] [PMID: 27759082]
[68]
Heo, J.H.; Yoon, J.A.; Ahn, E.K.; Kim, H.; Urm, S.H.; Oak, C.O.; Yu, B.C.; Lee, S.J. Intraperitoneal administration of adipose tissue‐derived stem cells for the rescue of retinal degeneration in a mouse model via indigenous CNTF up‐regulation by IL‐6. J. Tissue Eng. Regen. Med., 2018, 12(3), e1370-e1382.
[http://dx.doi.org/10.1002/term.2522] [PMID: 28715614]
[69]
Kent, T.L.; Glybina, I.V.; Abrams, G.W.; Iezzi, R. Chronic intravitreous infusion of ciliary neurotrophic factor modulates electrical retinal stimulation thresholds in the RCS rat. Invest. Ophthalmol. Vis. Sci., 2008, 49(1), 372-379.
[http://dx.doi.org/10.1167/iovs.07-0952] [PMID: 18172115]
[70]
Zhang, K.; Hopkins, J.J.; Heier, J.S.; Birch, D.G.; Halperin, L.S.; Albini, T.A.; Brown, D.M.; Jaffe, G.J.; Tao, W.; Williams, G.A. Ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for treatment of geographic atrophy in age-related macular degeneration. Proc. Natl. Acad. Sci. USA, 2011, 108(15), 6241-6245.
[http://dx.doi.org/10.1073/pnas.1018987108] [PMID: 21444807]
[71]
Bucher, F.; Walz, J.M.; Bühler, A.; Aguilar, E.; Lange, C.; Diaz-Aguilar, S.; Martin, G.; Schlunck, G.; Agostini, H.; Friedlander, M.; Stahl, A. CNTF attenuates vasoproliferative changes through upregulation of SOCS3 in a mouse-model of oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci., 2016, 57(10), 4017-4026.
[http://dx.doi.org/10.1167/iovs.15-18508] [PMID: 27494343]
[72]
Chew, E.Y.; Clemons, T.E.; Jaffe, G.J.; Johnson, C.A.; Farsiu, S.; Lad, E.M.; Guymer, R.; Rosenfeld, P.; Hubschman, J.P.; Constable, I.; Wiley, H.; Singerman, L.J.; Gillies, M.; Comer, G.; Blodi, B.; Eliott, D.; Yan, J.; Bird, A.; Friedlander, M. Effect of ciliary neurotrophic factor on retinal neurodegeneration in patients with macular telangiectasia type 2. Ophthalmology, 2019, 126(4), 540-549.
[http://dx.doi.org/10.1016/j.ophtha.2018.09.041] [PMID: 30292541]
[73]
Khodabande, A.; Roohipoor, R.; Zamani, J.; Mirghorbani, M.; Zolfaghari, H.; Karami, S.; Modjtahedi, B.S. Management of idiopathic macular telangiectasia type 2. Ophthalmol. Ther., 2019, 8(2), 155-175.
[http://dx.doi.org/10.1007/s40123-019-0170-1] [PMID: 30788805]
[74]
Sallo, F.B.; Leung, I.; Clemons, T.E.; Peto, T.; Chew, E.Y.; Pauleikhoff, D.; Bird, A.C. Correlation of structural and functional outcome measures in a phase one trial of ciliary neurotrophic factor in type 2 idiopathic macular telangiectasia. Retina, 2018, 38(1), S27-S32.
[http://dx.doi.org/10.1097/IAE.0000000000001706] [PMID: 28541963]
[75]
Duncan, J.L. Ciliary neurotrophic factor treatment improves retinal structure and function in macular telangiectasia type 2. Ophthalmology, 2019, 126(4), 550-551.
[http://dx.doi.org/10.1016/j.ophtha.2018.12.023] [PMID: 30910039]
[76]
Shpak, A.A.; Guekht, A.B.; Druzhkova, T.A.; Kozlova, K.I.; Gulyaeva, N.V. Ciliary neurotrophic factor in patients with primary open-angle glaucoma and age-related cataract. Mol. Vis., 2017, 23, 799-809.
[PMID: 29225456]
[77]
Chen, J.; Chen, P.; Backman, L.J.; Zhou, Q.; Danielson, P. Ciliary neurotrophic factor promotes the migration of corneal epithelial stem/progenitor cells by up-regulation of mmps through the phosphorylation of Akt. Sci. Rep., 2016, 6(1), 25870.
[http://dx.doi.org/10.1038/srep25870] [PMID: 27174608]
[78]
Ghasemi, M.; Alizadeh, E.; Motlagh, B.F.; Zarghami, N. The effect of exogenous ciliary neurotrophic factor on cell cycle and neural differentiation markers of in vitro model cells: New insights for future therapeutic approaches. Cell Biochem. Funct., 2021, 39(5), 636-645.
[http://dx.doi.org/10.1002/cbf.3628] [PMID: 33890305]
[79]
Si, Z.P.; Wang, G.; Han, S.S.; Jin, Y.; Hu, Y.X.; He, M.Y.; Brand-Saberi, B.; Yang, X.; Liu, G.S. CNTF and Nrf2 are coordinately involved in regulating self-renewal and differentiation of neural stem cell during embryonic development. iScience, 2019, 19, 303-315.
[http://dx.doi.org/10.1016/j.isci.2019.07.038] [PMID: 31404831]
[80]
Shimazaki, T.; Shingo, T.; Weiss, S. The ciliary neurotrophic factor/leukemia inhibitory factor/gp130 receptor complex operates in the maintenance of mammalian forebrain neural stem cells. J. Neurosci., 2001, 21(19), 7642-7653.
[http://dx.doi.org/10.1523/JNEUROSCI.21-19-07642.2001] [PMID: 11567054]
[81]
Jia, C.; Keasey, M.P.; Malone, H.M.; Lovins, C.; Sante, R.R.; Razskazovskiy, V.; Hagg, T. Vitronectin from brain pericytes promotes adult forebrain neurogenesis by stimulating CNTF. Exp. Neurol., 2019, 312, 20-32.
[http://dx.doi.org/10.1016/j.expneurol.2018.11.002] [PMID: 30408465]
[82]
Jia, C.; Keasey, M.P.; Lovins, C.; Hagg, T. Inhibition of astrocyte FAK–JNK signaling promotes subventricular zone neurogenesis through CNTF. Glia, 2018, 66(11), 2456-2469.
[http://dx.doi.org/10.1002/glia.23498] [PMID: 30500112]
[83]
de Leeuw, V.C.; van Oostrom, C.T.M.; Westerink, R.H.S.; Piersma, A.H.; Heusinkveld, H.J.; Hessel, E.V.S. An efficient neuron-astrocyte differentiation protocol from human embryonic stem cell-derived neural progenitors to assess chemical-induced developmental neurotoxicity. Reprod. Toxicol., 2020, 98, 107-116.
[http://dx.doi.org/10.1016/j.reprotox.2020.09.003] [PMID: 32931842]
[84]
Byun, J.S.; Lee, C.O.; Oh, M.; Cha, D.; Kim, W.K.; Oh, K.J.; Bae, K.H.; Lee, S.C.; Han, B.S. Rapid differentiation of astrocytes from human embryonic stem cells. Neurosci. Lett., 2020, 716, 134681.
[http://dx.doi.org/10.1016/j.neulet.2019.134681] [PMID: 31836568]
[85]
Zeng, S.; Zhao, X.; Zhang, L.; Pathak, J.L.; Huang, W.; Li, Y.; Guan, H.; Zhao, W.; Ge, L.; Shu, Y. Effect of ciliary neurotrophic factor on neural differentiation of stem cells of human exfoliated deciduous teeth. J. Biol. Eng., 2020, 14(1), 29.
[http://dx.doi.org/10.1186/s13036-020-00251-4] [PMID: 33298129]
[86]
Shirazi, H.A.; Rasouli, J.; Ciric, B.; Rostami, A.; Zhang, G.X. 1,25-Dihydroxyvitamin D3 enhances neural stem cell proliferation and oligodendrocyte differentiation. Exp. Mol. Pathol., 2015, 98(2), 240-245.
[http://dx.doi.org/10.1016/j.yexmp.2015.02.004] [PMID: 25681066]
[87]
Dobrowolski, M.; Cave, C.; Levy-Myers, R.; Lee, C.; Park, S.; Choi, B.R.; Xiao, B.; Yang, W.; Sockanathan, S. GDE3 regulates oligodendrocyte precursor proliferation via release of soluble CNTFRα. Development, 2020, 147(2), dev.180695.
[http://dx.doi.org/10.1242/dev.180695] [PMID: 31932351]
[88]
Gu, Y.L.; Gao, G.Q.; Ma, N.; Ye, L.L.; Zhang, L.W.; Gao, X.; Zhang, Z.B. CNTF protects neurons from hypoxic injury through the activation of STAT3pTyr705. Int. J. Mol. Med., 2016, 38(6), 1915-1921.
[http://dx.doi.org/10.3892/ijmm.2016.2769] [PMID: 27748830]
[89]
Beurrier, C.; Faideau, M.; Bennouar, K.E.; Escartin, C.; Kerkerian-Le Goff, L.; Bonvento, G.; Gubellini, P. Ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake. PLoS One, 2010, 5(1), e8550.
[http://dx.doi.org/10.1371/journal.pone.0008550] [PMID: 20062544]
[90]
Alpár, A.; Zahola, P.; Hanics, J.; Hevesi, Z.; Korchynska, S.; Benevento, M.; Pifl, C.; Zachar, G.; Perugini, J.; Severi, I.; Leitgeb, P.; Bakker, J.; Miklosi, A.G.; Tretiakov, E.; Keimpema, E.; Arque, G.; Tasan, R.O.; Sperk, G.; Malenczyk, K.; Máté, Z.; Erdélyi, F.; Szabó, G.; Lubec, G.; Palkovits, M.; Giordano, A.; Hökfelt, T.G.M.; Romanov, R.A.; Horvath, T.L.; Harkany, T. Hypothalamic CNTF volume transmission shapes cortical noradrenergic excitability upon acute stress. EMBO J., 2018, 37(21), 37.
[http://dx.doi.org/10.15252/embj.2018100087] [PMID: 30209240]
[91]
Escartin, C.; Pierre, K.; Colin, A.; Brouillet, E.; Delzescaux, T.; Guillermier, M.; Dhenain, M.; Déglon, N.; Hantraye, P.; Pellerin, L.; Bonvento, G. Activation of astrocytes by CNTF induces metabolic plasticity and increases resistance to metabolic insults. J. Neurosci., 2007, 27(27), 7094-7104.
[http://dx.doi.org/10.1523/JNEUROSCI.0174-07.2007] [PMID: 17611262]
[92]
Jeong, K.H.; Nam, J.H.; Jin, B.K.; Kim, S.R. Activation of CNTF/CNTFRα signaling pathway by hRheb(S16H) transduction of dopaminergic neurons in vivo. PLoS One, 2015, 10(3), e0121803.
[http://dx.doi.org/10.1371/journal.pone.0121803] [PMID: 25799580]
[93]
Udovin, L.; Quarracino, C.; Herrera, M.I.; Capani, F.; Otero-Losada, M.; Perez-Lloret, S. Role of astrocytic dysfunction in the pathogenesis of Parkinson’s disease animal models from a molecular signaling perspective. Neural Plast., 2020, 2020, 1-10.
[http://dx.doi.org/10.1155/2020/1859431] [PMID: 32089670]
[94]
Kim, K.I.; Baek, J.Y.; Jeong, J.Y.; Nam, J.H.; Park, E.S.; Bok, E.; Shin, W.H.; Chung, Y.C.; Jin, B.K. Delayed treatment of capsaicin produces partial motor recovery by enhancing dopamine function in MPP+ -lesioned rats via ciliary neurotrophic factor. Exp. Neurobiol., 2019, 28(2), 289-299.
[http://dx.doi.org/10.5607/en.2019.28.2.289] [PMID: 31138996]
[95]
Baek, J.; Jeong, J.; Kim, K.; Won, S.Y.; Chung, Y.; Nam, J.; Cho, E.; Ahn, T.B.; Bok, E.; Shin, W.H.; Jin, B. Inhibition of microglia-derived oxidative stress by ciliary neurotrophic factor protects dopamine neurons in vivo from MPP+ neurotoxicity. Int. J. Mol. Sci., 2018, 19(11), 3543.
[http://dx.doi.org/10.3390/ijms19113543] [PMID: 30423807]
[96]
Onyango, I.; Khan, S. Oxidative stress, mitochondrial dysfunction, and stress signaling in Alzheimer’s disease. Curr. Alzheimer Res., 2006, 3(4), 339-349.
[http://dx.doi.org/10.2174/156720506778249489] [PMID: 17017864]
[97]
Wang, K.; Xie, M.; Zhu, L.; Zhu, X.; Zhang, K.; Zhou, F. Ciliary neurotrophic factor protects SH-SY5Y neuroblastoma cells against Aβ 1-42-induced neurotoxicity via activating the JAK2/STAT3 axis. Folia Neuropathol., 2015, 3(3), 226-235.
[http://dx.doi.org/10.5114/fn.2015.54423] [PMID: 26443313]
[98]
Bali, P.; Banik, A.; Nehru, B.; Anand, A. Neurotrophic factors mediated activation of astrocytes ameliorate memory loss by amyloid clearance after transplantation of lineage negative stem cells. Mol. Neurobiol., 2019, 56(12), 8420-8434.
[http://dx.doi.org/10.1007/s12035-019-01680-z] [PMID: 31250384]
[99]
Jiang, H.; Tian, K.W.; Zhang, F.; Wang, B.; Han, S. Reg-2, A downstream signaling protein in the ciliary neurotrophic factor survival pathway, alleviates experimental autoimmune encephalomyelitis. Front. Neuroanat., 2016, 10, 50.
[http://dx.doi.org/10.3389/fnana.2016.00050] [PMID: 27242448]
[100]
Bechstein, M.; Häussler, U.; Neef, M.; Hofmann, H.D.; Kirsch, M.; Haas, C.A. CNTF-mediated preactivation of astrocytes attenuates neuronal damage and epileptiform activity in experimental epilepsy. Exp. Neurol., 2012, 236(1), 141-150.
[http://dx.doi.org/10.1016/j.expneurol.2012.04.009] [PMID: 22542945]
[101]
Leyton-Jaimes, M.F.; Ivert, P.; Hoeber, J.; Han, Y.; Feiler, A.; Zhou, C.; Pankratova, S.; Shoshan-Barmatz, V.; Israelson, A.; Kozlova, E.N. Empty mesoporous silica particles significantly delay disease progression and extend survival in a mouse model of ALS. Sci. Rep., 2020, 10(1), 20675.
[http://dx.doi.org/10.1038/s41598-020-77578-x] [PMID: 33244084]
[102]
Moradi, P.; Ganjkhani, M.; Anarkooli, I.J.; Abdanipour, A. Neuroprotective effects of lovastatin in the pilocarpine rat model of epilepsy according to the expression of neurotrophic factors. Metab. Brain Dis., 2019, 34(4), 1061-1069.
[http://dx.doi.org/10.1007/s11011-019-00424-1] [PMID: 31144103]
[103]
Shi, H.; Li, X.; Yang, J.; Zhao, Y.; Xue, C.; Wang, Y.; He, Q.; Shen, M.; Zhang, Q.; Yang, Y.; Ding, F. Bone marrow-derived neural crest precursors improve nerve defect repair partially through secreted trophic factors. Stem Cell Res. Ther., 2019, 10(1), 397.
[http://dx.doi.org/10.1186/s13287-019-1517-1] [PMID: 31852510]
[104]
Dziennis, S.; Habecker, B.A. Ciliary neurotrophic factor suppresses Phox2a in sympathetic neurons. Neuroreport, 2004, 15(1), 33-36.
[http://dx.doi.org/10.1097/00001756-200401190-00008] [PMID: 15106827]
[105]
Shi, X.; Woodward, W.R.; Habecker, B.A. Ciliary neurotrophic factor stimulates tyrosine hydroxylase activity. J. Neurochem., 2012, 121(5), 700-704.
[http://dx.doi.org/10.1111/j.1471-4159.2012.07712.x] [PMID: 22372951]
[106]
Stegenga, S.L.; Hirayama, K.; Kapatos, G. Regulation of GTP cyclohydrolase I gene expression and tetrahydrobiopterin content in cultured sympathetic neurons by leukemia inhibitory factor and ciliary neurotrophic factor. J. Neurochem., 1996, 66(6), 2541-2545.
[http://dx.doi.org/10.1046/j.1471-4159.1996.66062541.x] [PMID: 8632180]
[107]
Slonimsky, J.; Yang, B.; Hinterneder, J.M.; Nokes, E.B.; Birren, S.J. BDNF and CNTF regulate cholinergic properties of sympathetic neurons through independent mechanisms. Mol. Cell. Neurosci., 2003, 23(4), 648-660.
[http://dx.doi.org/10.1016/S1044-7431(03)00102-7] [PMID: 12932444]
[108]
Xing, Y.; Wen, S.; Li, A.; Mi, K.; Wang, R.; Li, H.; Liu, H. in vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity. Neural Regen. Res., 2017, 12(10), 1716-1723.
[http://dx.doi.org/10.4103/1673-5374.217352] [PMID: 29171438]
[109]
Gallagher, D.; Gutierrez, H.; Gavalda, N.; O’Keeffe, G.; Hay, R.; Davies, A.M. Nuclear factor-kappaB activation via tyrosine phosphorylation of inhibitor kappaB-alpha is crucial for ciliary neurotrophic factor-promoted neurite growth from developing neurons. J. Neurosci., 2007, 27(36), 9664-9669.
[http://dx.doi.org/10.1523/JNEUROSCI.0608-07.2007] [PMID: 17804627]
[110]
Saleh, A.; Roy Chowdhury, S.K.; Smith, D.R.; Balakrishnan, S.; Tessler, L.; Martens, C.; Morrow, D.; Schartner, E.; Frizzi, K.E.; Calcutt, N.A.; Fernyhough, P. Ciliary neurotrophic factor activates NF-κB to enhance mitochondrial bioenergetics and prevent neuropathy in sensory neurons of streptozotocin-induced diabetic rodents. Neuropharmacology, 2013, 65, 65-73.
[http://dx.doi.org/10.1016/j.neuropharm.2012.09.015] [PMID: 23022047]
[111]
Chowdhury, S.R.; Saleh, A.; Akude, E.; Smith, D.R.; Morrow, D.; Tessler, L.; Calcutt, N.A.; Fernyhough, P. Ciliary neurotrophic factor reverses aberrant mitochondrial bioenergetics through the JAK/STAT pathway in cultured sensory neurons derived from streptozotocin-induced diabetic rodents. Cell. Mol. Neurobiol., 2014, 34(5), 643-649.
[http://dx.doi.org/10.1007/s10571-014-0054-9] [PMID: 24682898]
[112]
Hu, Z.; Deng, N.; Liu, K.; Zhou, N.; Sun, Y.; Zeng, W. CNTF-STAT3-IL-6 axis mediates neuroinflammatory cascade across schwann cell-neuron-microglia. Cell Rep., 2020, 31(7), 107657.
[http://dx.doi.org/10.1016/j.celrep.2020.107657] [PMID: 32433966]
[113]
Darvishi, M.; Tiraihi, T.; Mesbah-Namin, S.A.; Delshad, A.; Taheri, T. Motor neuron transdifferentiation of neural stem cell from adipose-derived stem cell characterized by differential gene expression. Cell. Mol. Neurobiol., 2017, 37(2), 275-289.
[http://dx.doi.org/10.1007/s10571-016-0368-x] [PMID: 27107758]
[114]
Schaller, S.; Buttigieg, D.; Alory, A.; Jacquier, A.; Barad, M.; Merchant, M.; Gentien, D.; de la Grange, P.; Haase, G. Novel combinatorial screening identifies neurotrophic factors for selective classes of motor neurons. Proc. Natl. Acad. Sci. USA, 2017, 114(12), E2486-E2493.
[http://dx.doi.org/10.1073/pnas.1615372114] [PMID: 28270618]
[115]
Lee, N.; Spearry, R.P.; Leahy, K.M.; Robitz, R.; Trinh, D.S.; Mason, C.O.; Zurbrugg, R.J.; Batt, M.K.; Paul, R.J.; Maclennan, A.J. Muscle ciliary neurotrophic factor receptor α promotes axonal regeneration and functional recovery following peripheral nerve lesion. J. Comp. Neurol., 2013, 521(13), 2947-2965.
[http://dx.doi.org/10.1002/cne.23324] [PMID: 23504871]
[116]
Cui, W.; Liu, C.X.; Wang, J.; Zhang, Y.C.; Shen, Q.; Feng, Z.H.; Wu, J.; Li, J.X. An oleanolic acid derivative reduces denervation-induced muscle atrophy via activation of CNTF-mediated JAK2/STAT3 signaling pathway. Eur. J. Pharmacol., 2019, 861, 172612.
[http://dx.doi.org/10.1016/j.ejphar.2019.172612] [PMID: 31421088]
[117]
Jia, C.; Oliver, J.; Gilmer, D.; Lovins, C.; Rodriguez-Gil, D.J.; Hagg, T. Inhibition of focal adhesion kinase increases adult olfactory stem cell self-renewal and neuroregeneration through ciliary neurotrophic factor. Stem Cell Res. (Amst.), 2020, 49, 102061.
[http://dx.doi.org/10.1016/j.scr.2020.102061] [PMID: 33130470]
[118]
Xu, B.; Xie, X. Neurotrophic factor control of satiety and body weight. Nat. Rev. Neurosci., 2016, 17(5), 282-292.
[http://dx.doi.org/10.1038/nrn.2016.24] [PMID: 27052383]
[119]
Venema, W.; Severi, I.; Perugini, J.; Di Mercurio, E.; Mainardi, M.; Maffei, M.; Cinti, S.; Giordano, A. Ciliary neurotrophic factor acts on distinctive hypothalamic arcuate neurons and promotes leptin entry into and action on the mouse hypothalamus. Front. Cell. Neurosci., 2020, 14, 140.
[http://dx.doi.org/10.3389/fncel.2020.00140] [PMID: 32528252]
[120]
Gloaguen, I.; Costa, P.; Demartis, A.; Lazzaro, D.; Di Marco, A.; Graziani, R.; Paonessa, G.; Chen, F.; Rosenblum, C.I.; Van der Ploeg, L.H.T.; Cortese, R.; Ciliberto, G.; Laufer, R. Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin deficiency and resistance. Proc. Natl. Acad. Sci. USA, 1997, 94(12), 6456-6461.
[http://dx.doi.org/10.1073/pnas.94.12.6456] [PMID: 9177239]
[121]
Lambert, P.D.; Anderson, K.D.; Sleeman, M.W.; Wong, V.; Tan, J.; Hijarunguru, A.; Corcoran, T.L.; Murray, J.D.; Thabet, K.E.; Yancopoulos, G.D.; Wiegand, S.J. Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity. Proc. Natl. Acad. Sci. USA, 2001, 98(8), 4652-4657.
[http://dx.doi.org/10.1073/pnas.061034298] [PMID: 11259650]
[122]
Pascual-Gamarra, J.M.; Salazar-Tortosa, D.F.; Labayen, I.; Rupérez, A.I.; Censi, L.; Béghin, L.; Michels, N.; Gonzalez-Gross, M.; Manios, Y.; Lambrinou, C.P.; Moreno, L.A.; Meirhaeghe, A.; Castillo, M.J.; Ruiz, J.R. Association between CNTF polymorphisms and adiposity markers in european adolescents. J. Pediatr., 2020, 219, 23-30.e1.
[http://dx.doi.org/10.1016/j.jpeds.2019.12.036] [PMID: 32037156]
[123]
Lemper, M.; De Groef, S.; Stangé, G.; Baeyens, L.; Heimberg, H. A combination of cytokines EGF and CNTF protects the functional beta cell mass in mice with short-term hyperglycaemia. Diabetologia, 2016, 59(9), 1948-1958.
[http://dx.doi.org/10.1007/s00125-016-4023-3] [PMID: 27318836]
[124]
André, C.; Catania, C.; Remus-Borel, J.; Ladeveze, E.; Leste-Lasserre, T.; Mazier, W.; Binder, E.; Gonzales, D.; Clark, S.; Guzman-Quevedo, O.; Abrous, D.N.; Layé, S.; Cota, D. mTORC1 pathway disruption abrogates the effects of the ciliary neurotrophic factor on energy balance and hypothalamic neuroinflammation. Brain Behav. Immun., 2018, 70, 325-334.
[http://dx.doi.org/10.1016/j.bbi.2018.03.014] [PMID: 29548998]
[125]
Senzacqua, M.; Severi, I.; Perugini, J.; Acciarini, S.; Cinti, S.; Giordano, A. Action of administered ciliary neurotrophic factor on the mouse dorsal vagal complex. Front. Neurosci., 2016, 10, 289.
[http://dx.doi.org/10.3389/fnins.2016.00289] [PMID: 27445662]
[126]
Ott, V.; Fasshauer, M.; Dalski, A.; Klein, H.H.; Klein, J. Direct effects of ciliary neurotrophic factor on brown adipocytes: Evidence for a role in peripheral regulation of energy homeostasis. J. Endocrinol., 2002, 173(2), R1-R8.
[http://dx.doi.org/10.1677/joe.0.173r001] [PMID: 12010646]
[127]
Zvonic, S.; Cornelius, P.; Stewart, W.C.; Mynatt, R.L.; Stephens, J.M. The regulation and activation of ciliary neurotrophic factor signaling proteins in adipocytes. J. Biol. Chem., 2003, 278(4), 2228-2235.
[http://dx.doi.org/10.1074/jbc.M205871200] [PMID: 12424252]
[128]
Perugini, J.; Di Mercurio, E.; Tossetta, G.; Severi, I.; Monaco, F.; Reguzzoni, M.; Tomasetti, M.; Dani, C.; Cinti, S.; Giordano, A. Biological effects of ciliary neurotrophic factor on hMADS adipocytes. Front. Endocrinol. (Lausanne), 2019, 10, 768.
[http://dx.doi.org/10.3389/fendo.2019.00768] [PMID: 31781039]
[129]
Tsompanidis, A.; Vafiadaki, E.; Blüher, S.; Kalozoumi, G.; Sanoudou, D.; Mantzoros, C.S. Ciliary neurotrophic factor upregulates follistatin and Pak1, causes overexpression of muscle differentiation related genes and downregulation of established atrophy mediators in skeletal muscle. Metabolism, 2016, 65(6), 915-925.
[http://dx.doi.org/10.1016/j.metabol.2016.03.005] [PMID: 27173470]
[130]
Watt, M.J.; Dzamko, N.; Thomas, W.G.; Rose-John, S.; Ernst, M.; Carling, D.; Kemp, B.E.; Febbraio, M.A.; Steinberg, G.R. CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat. Med., 2006, 12(5), 541-548.
[http://dx.doi.org/10.1038/nm1383] [PMID: 16604088]
[131]
Steinberg, G.R.; Watt, M.J.; Ernst, M.; Birnbaum, M.J.; Kemp, B.E.; Jørgensen, S.B. Ciliary neurotrophic factor stimulates muscle glucose uptake by a PI3-kinase-dependent pathway that is impaired with obesity. Diabetes, 2009, 58(4), 829-839.
[http://dx.doi.org/10.2337/db08-0659] [PMID: 19136654]
[132]
Bise, T.; de Preux Charles, A.S.; Jaźwińska, A. Ciliary neurotrophic factor stimulates cardioprotection and the proliferative activity in the adult zebrafish heart. NPJ Regen. Med., 2019, 4(1), 2.
[http://dx.doi.org/10.1038/s41536-019-0064-9] [PMID: 30701084]
[133]
Zheng, K.; Zhang, Q.; Sheng, Z.; Li, Y.; Lu, H. Ciliary neurotrophic factor (CNTF) protects myocardial cells from oxygen glucose deprivation (OGD)/re-oxygenation via activation of Akt-Nrf2 signaling. Cell. Physiol. Biochem., 2018, 51(4), 1852-1862.
[http://dx.doi.org/10.1159/000495711] [PMID: 30504707]
[134]
Zhong, P.; Zeng, G.; Lei, C.; Tian, G.; Ouyang, S.; Liu, F.; Peng, J. Ciliary neurotrophic factor overexpression protects the heart against pathological remodelling in angiotensin II-infused mice. Biochem. Biophys. Res. Commun., 2021, 547, 15-22.
[http://dx.doi.org/10.1016/j.bbrc.2021.01.111] [PMID: 33588234]
[135]
Zhong, P.; Peng, J.; Liu, T.; Ding, H.S. AAV9-mediated cardiac CNTF overexpression exacerbated adverse cardiac remodeling in streptozotocin-induced type 1 diabetic models. Cardiovasc. Toxicol., 2021, 22(1), 88-96.
[PMID: 34674150]
[136]
Brondino, N.; Rocchetti, M.; Fusar-Poli, L.; Damiani, S.; Goggi, A.; Chiodelli, G.; Corti, S.; Visai, L.; Politi, P. Increased CNTF levels in adults with autism spectrum disorders. World J. Biol. Psychiatry, 2019, 20(9), 742-746.
[http://dx.doi.org/10.1080/15622975.2018.1481999] [PMID: 29869578]
[137]
Jia, C.; Brown, R.W.; Malone, H.M.; Burgess, K.C.; Gill, W.D.; Keasey, M.P.; Hagg, T. Ciliary neurotrophic factor is a key sex-specific regulator of depressive-like behavior in mice. Psychoneuroendocrinology, 2019, 100, 96-105.
[http://dx.doi.org/10.1016/j.psyneuen.2018.09.038] [PMID: 30299260]
[138]
Shpak, A.; Guekht, A.; Druzhkova, T.; Rider, F.; Gudkova, A.; Gulyaeva, N. Increased ciliary neurotrophic factor in blood serum and lacrimal fluid as a potential biomarkers of focal epilepsy. Neurol. Sci., 2022, 43(1), 493-498.
[PMID: 34031798]
[139]
Girotti, M.; Silva, J.D.; George, C.M.; Morilak, D.A. Ciliary neurotrophic factor signaling in the rat orbitofrontal cortex ameliorates stress-induced deficits in reversal learning. Neuropharmacology, 2019, 160, 107791.
[http://dx.doi.org/10.1016/j.neuropharm.2019.107791] [PMID: 31553898]
[140]
Alvim, M.K.M.; Morita-Sherman, M.E.; Yasuda, C.L.; Rocha, N.P.; Vieira, É.L.; Pimentel-Silva, L.R.; Henrique Nogueira, M.; Barbosa, R.; Watanabe, N.; Coan, A.C.; Lopes-Cendes, I.; Teixeira, A.L.; Cendes, F. Inflammatory and neurotrophic factor plasma levels are related to epilepsy independently of etiology. Epilepsia, 2021, 62(10), 2385-2394.
[http://dx.doi.org/10.1111/epi.17023] [PMID: 34331458]
[141]
Liu, H.; Tan, N.; Xu, D.; Li, C.Y.; Xian, G.J. NGF and CNTF expression and regulation mechanism by miRNA in acute paralytic strabismus. Int. Ophthalmol., 2020, 40(4), 975-984.
[http://dx.doi.org/10.1007/s10792-019-01270-x] [PMID: 31925656]
[142]
Gresle, M.M.; Alexandrou, E.; Wu, Q.; Egan, G.; Jokubaitis, V.; Ayers, M.; Jonas, A.; Doherty, W.; Friedhuber, A.; Shaw, G.; Sendtner, M.; Emery, B.; Kilpatrick, T.; Butzkueven, H. Leukemia inhibitory factor protects axons in experimental autoimmune encephalomyelitis via an oligodendrocyte-independent mechanism. PLoS One, 2012, 7(10), e47379.
[http://dx.doi.org/10.1371/journal.pone.0047379] [PMID: 23077604]
[143]
Blanco, R.E.; Vega-Meléndez, G.S.; De La Rosa-Reyes, V.; del Cueto, C.; Blagburn, J.M. Application of CNTF or FGF-2 increases the number of M2-like macrophages after optic nerve injury in adult Rana pipiens. PLoS One, 2019, 14(5), e0209733.
[http://dx.doi.org/10.1371/journal.pone.0209733] [PMID: 31048836]
[144]
Fantone, S.; Tossetta, G.; Montironi, R.; Senzacqua, M.; Marzioni, D.; Mazzucchelli, R. Ciliary neurotrophic factor (CNTF) and its receptor (CNTFRα) signal through MAPK/ERK pathway in human prostate tissues: A morphological and biomolecular study. Eur. J. Histochem., 2020, 64(4), 64.
[http://dx.doi.org/10.4081/ejh.2020.3147] [PMID: 33131268]

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