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Protein & Peptide Letters

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

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Review Article

A Review of Gap Junction Protein and its Potential Role in Nervous System-Related Disease

Author(s): Qiong Xiang, Xiao-Lin Liu, Jia-Jia Chen, Liang Yang, Li-Ni Liu, Jing Deng, Jia-Sheng Tao and Xian-Hui Li*

Volume 30, Issue 11, 2023

Published on: 16 November, 2023

Page: [891 - 899] Pages: 9

DOI: 10.2174/0109298665269246231023104904

Price: $65

Abstract

Gap junction (GJ) is a special cell membrane structure composed of connexin. Connexin is widely distributed and expressed in all tissues except differentiated skeletal muscle, red blood cells, and mature sperm cells, which is related to the occurrence of many genetic diseases due to its mutation. Its function of regulating immune response, cell proliferation, migration, apoptosis, and carcinogenesis makes it a therapeutic target for a variety of diseases. In this paper, the possible mechanism of its action in nervous system-related diseases and treatment are reviewed.

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[1]
Nielsen, M.S.; Axelsen, L.N.; Sorgen, P.L.; Verma, V.; Delmar, M.; Holstein-Rathlou, N.H. Gap junctions. Compr. Physiol., 2012, 2(3), 1981-2035.
[http://dx.doi.org/10.1002/cphy.c110051] [PMID: 23723031]
[2]
Qiu, Y.; Zheng, J.; Chen, S.; Sun, Y. Connexin mutations and hereditary diseases. Int. J. Mol. Sci., 2022, 23(8), 4255.
[http://dx.doi.org/10.3390/ijms23084255] [PMID: 35457072]
[3]
Zhou, J.Z.; Jiang, J.X. Gap junction and hemichannel-independent actions of connexins on cell and tissue functions - An update. FEBS Lett., 2014, 588(8), 1186-1192.
[http://dx.doi.org/10.1016/j.febslet.2014.01.001] [PMID: 24434539]
[4]
Oshima, A. Structure of an innexin gap junction channel and cryo-EM sample preparation. Microscopy (Oxf.), 2017, 66(6), 371-379.
[http://dx.doi.org/10.1093/jmicro/dfx035] [PMID: 29036409]
[5]
Bruzzone, R.; White, T.W.; Paul, D.L. Connections with connexins: The molecular basis of direct intercellular signaling. Eur. J. Biochem., 1996, 238(1), 1-27.
[http://dx.doi.org/10.1111/j.1432-1033.1996.0001q.x] [PMID: 8665925]
[6]
Maeda, S.; Tsukihara, T. Structure of the gap junction channel and its implications for its biological functions. Cell. Mol. Life Sci., 2011, 68(7), 1115-1129.
[http://dx.doi.org/10.1007/s00018-010-0551-z] [PMID: 20960023]
[7]
Baker, M.W.; Macagno, E.R. Gap junction proteins and the wiring (Rewiring) of neuronal circuits. Dev. Neurobiol., 2017, 77(5), 575-586.
[http://dx.doi.org/10.1002/dneu.22429] [PMID: 27512961]
[8]
Graham, S.; Jiang, J.; Mesnil, M. Connexins and pannexins: Important players in tumorigenesis, metastasis and potential therapeutics. Int. J. Mol. Sci., 2018, 19(6), 1645.
[http://dx.doi.org/10.3390/ijms19061645] [PMID: 29865195]
[9]
Delmar, M.; Laird, D.W.; Naus, C.C.; Nielsen, M.S.; Verselis, V.K.; White, T.W. Connexins and disease. Cold Spring Harb. Perspect. Biol., 2018, 10(9), a029348.
[http://dx.doi.org/10.1101/cshperspect.a029348] [PMID: 28778872]
[10]
Lambiase, P.D.; Tinker, A. Connexins in the heart. Cell Tissue Res., 2015, 360(3), 675-684.
[http://dx.doi.org/10.1007/s00441-014-2020-8] [PMID: 25358402]
[11]
Wong, P.; Tan, T.; Chan, C.; Laxton, V.; Chan, Y.W.F.; Liu, T.; Wong, W.T.; Tse, G. The role of connexins in wound healing and repair: Novel therapeutic approaches. Front. Physiol., 2016, 7, 596.
[http://dx.doi.org/10.3389/fphys.2016.00596] [PMID: 27999549]
[12]
Hu, X.; Yu, G.; Liao, X.; Xiao, L. Interactions between astrocytes and oligodendroglia in myelin development and related brain diseases. Neurosci. Bull., 2023, 39(3), 541-552.
[http://dx.doi.org/10.1007/s12264-022-00981-z] [PMID: 36370324]
[13]
Talukdar, S.; Emdad, L.; Das, S.K.; Fisher, P.B. GAP junctions: multifaceted regulators of neuronal differentiation. Tissue Barriers, 2022, 10(1), 1982349.
[http://dx.doi.org/10.1080/21688370.2021.1982349] [PMID: 34651545]
[14]
Imbeault, S.; Gauvin, L.G.; Toeg, H.D.; Pettit, A.; Sorbara, C.D.; Migahed, L.; DesRoches, R.; Menzies, A.S.; Nishii, K.; Paul, D.L.; Simon, A.M.; Bennett, S.A.L. The extracellular matrix controls gap junction protein expression and function in postnatal hippocampal neural progenitor cells. BMC Neurosci., 2009, 10(1), 13.
[http://dx.doi.org/10.1186/1471-2202-10-13] [PMID: 19236721]
[15]
Wang, Z.; Qian, D.; Zhu, W.; Hu, M.; Qin, Z.; Zhang, X.; Liu, M.; Wang, B. Cx43 and NMDA receptors changes in UL122 genetically modified mice hippocampus: a mechanism for spatial memory impairment. Int. J. Clin. Exp. Pathol., 2018, 11(1), 129-137.
[PMID: 31938094]
[16]
Koulakoff, A.; Mei, X.; Orellana, J.A.; Sáez, J.C.; Giaume, C. Glial connexin expression and function in the context of Alzheimer’s disease. Biochim. Biophys. Acta Biomembr., 2012, 1818(8), 2048-2057.
[http://dx.doi.org/10.1016/j.bbamem.2011.10.001] [PMID: 22008509]
[17]
Deshpande, T.; Li, T.; Henning, L.; Wu, Z.; Müller, J.; Seifert, G.; Steinhäuser, C.; Bedner, P. Constitutive deletion of astrocytic connexins aggravates kainate-induced epilepsy. Glia, 2020, 68(10), 2136-2147.
[http://dx.doi.org/10.1002/glia.23832] [PMID: 32240558]
[18]
Charvériat, M.; Mouthon, F.; Rein, W.; Verkhratsky, A. Connexins as therapeutic targets in neurological and neuropsychiatric disorders. Biochim. Biophys. Acta Mol. Basis Dis., 2021, 1867(5), 166098.
[http://dx.doi.org/10.1016/j.bbadis.2021.166098] [PMID: 33545299]
[19]
Nagy, J.I.; Ionescu, A.V.; Lynn, B.D.; Rash, J.E. Coupling of astrocyte connexins Cx26, Cx30, Cx43 to oligodendrocyte Cx29, Cx32, Cx47: Implications from normal and connexin32 knockout mice. Glia, 2003, 44(3), 205-218.
[http://dx.doi.org/10.1002/glia.10278] [PMID: 14603462]
[20]
David, D.J.; Samuels, B.A.; Rainer, Q.; Wang, J.W.; Marsteller, D.; Mendez, I.; Drew, M.; Craig, D.A.; Guiard, B.P.; Guilloux, J.P.; Artymyshyn, R.P.; Gardier, A.M.; Gerald, C.; Antonijevic, I.A.; Leonardo, E.D.; Hen, R. Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression. Neuron, 2009, 62(4), 479-493.
[http://dx.doi.org/10.1016/j.neuron.2009.04.017] [PMID: 19477151]
[21]
Chever, O.; Lee, C.Y.; Rouach, N. Astroglial connexin43 hemichannels tune basal excitatory synaptic transmission. J. Neurosci., 2014, 34(34), 11228-11232.
[http://dx.doi.org/10.1523/JNEUROSCI.0015-14.2014] [PMID: 25143604]
[22]
Ezan, P.; André, P.; Cisternino, S.; Saubaméa, B.; Boulay, A.C.; Doutremer, S.; Thomas, M.A.; Quenech’du, N.; Giaume, C.; Cohen-Salmon, M. Deletion of astroglial connexins weakens the blood-brain barrier. J. Cereb. Blood Flow Metab., 2012, 32(8), 1457-1467.
[http://dx.doi.org/10.1038/jcbfm.2012.45] [PMID: 22472609]
[23]
Hanslik, K.L.; Marino, K.M.; Ulland, T.K. Modulation of glial function in health, aging, and neurodegenerative disease. Front. Cell. Neurosci., 2021, 15, 718324.
[http://dx.doi.org/10.3389/fncel.2021.718324] [PMID: 34531726]
[24]
Fellin, T. Communication between neurons and astrocytes: relevance to the modulation of synaptic and network activity. J. Neurochem., 2009, 108(3), 533-544.
[http://dx.doi.org/10.1111/j.1471-4159.2008.05830.x] [PMID: 19187090]
[25]
Dere, E.; Zlomuzica, A. The role of gap junctions in the brain in health and disease. Neurosci. Biobehav. Rev., 2012, 36(1), 206-217.
[http://dx.doi.org/10.1016/j.neubiorev.2011.05.015] [PMID: 21664373]
[26]
Takeuchi, H.; Mizoguchi, H.; Doi, Y.; Jin, S.; Noda, M.; Liang, J.; Li, H.; Zhou, Y.; Mori, R.; Yasuoka, S.; Li, E.; Parajuli, B.; Kawanokuchi, J.; Sonobe, Y.; Sato, J.; Yamanaka, K.; Sobue, G.; Mizuno, T.; Suzumura, A. Blockade of gap junction hemichannel suppresses disease progression in mouse models of amyotrophic lateral sclerosis and Alzheimer’s disease. PLoS One, 2011, 6(6), e21108.
[http://dx.doi.org/10.1371/journal.pone.0021108] [PMID: 21712989]
[27]
Wroblewska-Seniuk, K.E.; Dabrowski, P.; Szyfter, W.; Mazela, J. Universal newborn hearing screening: methods and results, obstacles, and benefits. Pediatr. Res., 2017, 81(3), 415-422.
[http://dx.doi.org/10.1038/pr.2016.250] [PMID: 27861465]
[28]
Dai, P.; Huang, L.H.; Wang, G.J.; Gao, X.; Qu, C.Y.; Chen, X.W.; Ma, F.R.; Zhang, J.; Xing, W.L.; Xi, S.Y.; Ma, B.R.; Pan, Y.; Cheng, X.H.; Duan, H.; Yuan, Y.Y.; Zhao, L.P.; Chang, L.; Gao, R.Z.; Liu, H.H.; Zhang, W.; Huang, S.S.; Kang, D.Y.; Liang, W.; Zhang, K.; Jiang, H.; Guo, Y.L.; Zhou, Y.; Zhang, W.X.; Lyu, F.; Jin, Y.N.; Zhou, Z.; Lu, H.L.; Zhang, X.; Liu, P.; Ke, J.; Hao, J.S.; Huang, H.M.; Jiang, D.; Ni, X.; Long, M.; Zhang, L.; Qiao, J.; Morton, C.C.; Liu, X.Z.; Cheng, J.; Han, D.M. Concurrent hearing and genetic screening of 180,469 neonates with follow-up in Beijing, China. Am. J. Hum. Genet., 2019, 105(4), 803-812.
[http://dx.doi.org/10.1016/j.ajhg.2019.09.003] [PMID: 31564438]
[29]
Wu, J.; Cao, Z.; Su, Y.; Wang, Y.; Cai, R.; Chen, J.; Gao, B.; Han, M.; Li, X.; Zhang, D.; Gao, X.; Huang, S.; Huang, Q.; Yuan, Y.; Ma, X.; Dai, P. Molecular diagnose of a large hearing loss population from China by targeted genome sequencing. J. Hum. Genet., 2022, 67(11), 643-649.
[http://dx.doi.org/10.1038/s10038-022-01066-5] [PMID: 35982127]
[30]
Svidnicki, M.C.C.C.C.M.; Silva-Costa, S.M.; Ramos, P.Z.; dos Santos, N.Z.P.; Martins, F.T.A.; Castilho, A.M.; Sartorato, E.L. Screening of genetic alterations related to non-syndromic hearing loss using MassARRAY iPLEX® technology. BMC Med. Genet., 2015, 16(1), 85.
[http://dx.doi.org/10.1186/s12881-015-0232-8] [PMID: 26399936]
[31]
Su, H.A.; Lai, T.W.; Li, S.Y.; Su, T.R.; Yang, J.J.; Su, C.C. The functional role of CONNEXIN 26 mutation in nonsyndromic hearing loss, demonstrated by zebrafish connexin 30.3 homologue model. Cells, 2020, 9(5), 1291.
[http://dx.doi.org/10.3390/cells9051291] [PMID: 32455934]
[32]
Chen, P.; Wu, W.; Zhang, J.; Chen, J.; Li, Y.; Sun, L.; Hou, S.; Yang, J. Pathological mechanisms of connexin26-related hearing loss: Potassium recycling, ATP-calcium signaling, or energy supply? Front. Mol. Neurosci., 2022, 15, 976388.
[http://dx.doi.org/10.3389/fnmol.2022.976388] [PMID: 36187349]
[33]
Salt, A.N.; Hirose, K. Communication pathways to and from the inner ear and their contributions to drug delivery. Hear. Res., 2018, 362, 25-37.
[http://dx.doi.org/10.1016/j.heares.2017.12.010] [PMID: 29277248]
[34]
Nickel, R.; Forge, A. Gap junctions and connexins in the inner ear: their roles in homeostasis and deafness. Curr. Opin. Otolaryngol. Head Neck Surg., 2008, 16(5), 452-457.
[http://dx.doi.org/10.1097/MOO.0b013e32830e20b0] [PMID: 18797288]
[35]
Guo, J.; Ma, X.; Skidmore, J.M.; Cimerman, J.; Prieskorn, D.M.; Beyer, L.A.; Swiderski, D.L.; Dolan, D.F.; Martin, D.M.; Raphael, Y. GJB2 gene therapy and conditional deletion reveal developmental stage-dependent effects on inner ear structure and function. Mol. Ther. Methods Clin. Dev., 2021, 23, 319-333.
[http://dx.doi.org/10.1016/j.omtm.2021.09.009] [PMID: 34729379]
[36]
Hegde, S.; Hegde, R.; Kulkarni, S.S.; Das, K.K.; Gai, P.B.; Bulagouda, R.S. Analysis of genetic variations in connexin 26 (GJB2) gene among nonsyndromic hearing impairment: Familial study. Global Medical Genetics, 2022, 9(2), 152-158.
[http://dx.doi.org/10.1055/s-0042-1743257] [PMID: 35707775]
[37]
Chen, J.; Chen, J.; Zhu, Y.; Liang, C.; Zhao, H.B. Deafness induced by Connexin 26 (GJB2) deficiency is not determined by endocochlear potential (EP) reduction but is associated with cochlear developmental disorders. Biochem. Biophys. Res. Commun., 2014, 448(1), 28-32.
[http://dx.doi.org/10.1016/j.bbrc.2014.04.016] [PMID: 24732355]
[38]
Sellitto, C.; Li, L.; White, T.W. Connexin hemichannel inhibition ameliorates epidermal pathology in a mouse model of keratitis ichthyosis deafness syndrome. Sci. Rep., 2021, 11(1), 24118.
[http://dx.doi.org/10.1038/s41598-021-03627-8] [PMID: 34916582]
[39]
Zhao, H.B. Hypothesis of K+-recycling defect is not a primary deafness mechanism for Cx26 (GJB2) deficiency. Front. Mol. Neurosci., 2017, 10, 162.
[http://dx.doi.org/10.3389/fnmol.2017.00162] [PMID: 28603488]
[40]
Martínez, A.D.; Acuña, R.; Figueroa, V.; Maripillan, J.; Nicholson, B. Gap-junction channels dysfunction in deafness and hearing loss. Antioxid. Redox Signal., 2009, 11(2), 309-322.
[http://dx.doi.org/10.1089/ars.2008.2138] [PMID: 18837651]
[41]
Zhu, Y.; Chen, J.; Liang, C.; Zong, L.; Chen, J.; Jones, R.O.; Zhao, H.B. Connexin26 (GJB2) deficiency reduces active cochlear amplification leading to late-onset hearing loss. Neuroscience, 2015, 284, 719-729.
[http://dx.doi.org/10.1016/j.neuroscience.2014.10.061] [PMID: 25451287]
[42]
Youssefian, L.; Vahidnezhad, H.; Saeidian, A.H.; Mahmoudi, H.; Karamzadeh, R.; Kariminejad, A.; Huang, J.; Li, L.; Jannace, T.F.; Fortina, P.; Zeinali, S.; White, T.W.; Uitto, J. A novel autosomal recessive GJB2 -associated disorder: Ichthyosis follicularis, bilateral severe sensorineural hearing loss, and punctate palmoplantar keratoderma. Hum. Mutat., 2019, 40(2), 217-229.
[http://dx.doi.org/10.1002/humu.23686] [PMID: 30431684]
[43]
Locher, H.; de Groot, J.C.M.J.; van Iperen, L.; Huisman, M.A.; Frijns, J.H.M.; Chuva de Sousa Lopes, S.M. Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss. Dev. Neurobiol., 2015, 75(11), 1219-1240.
[http://dx.doi.org/10.1002/dneu.22279] [PMID: 25663387]
[44]
Sziklai, I. The significance of the calcium signal in the outer hair cells and its possible role in tinnitus of cochlear origin. Eur. Arch. Otorhinolaryngol., 2004, 261(10), 517-525.
[http://dx.doi.org/10.1007/s00405-004-0745-9] [PMID: 15609110]
[45]
Richard, E.M.; Maurice, T.; Delprat, B. Calcium signaling and genetic rare diseases: An auditory perspective. Cell Calcium, 2023, 110, 102702.
[http://dx.doi.org/10.1016/j.ceca.2023.102702] [PMID: 36791536]
[46]
Sirko, P.; Gale, J.E.; Ashmore, J.F. Intercellular Ca 2+ signalling in the adult mouse cochlea. J. Physiol., 2019, 597(1), 303-317.
[http://dx.doi.org/10.1113/JP276400] [PMID: 30318615]
[47]
Zheng, J.Q.; Poo, M. Calcium signaling in neuronal motility. Annu. Rev. Cell Dev. Biol., 2007, 23(1), 375-404.
[http://dx.doi.org/10.1146/annurev.cellbio.23.090506.123221] [PMID: 17944572]
[48]
Zhang, J.; Liang, Y.; Bradford, W.H.; Sheikh, F. Desmosomes: emerging pathways and non-canonical functions in cardiac arrhythmias and disease. Biophys. Rev., 2021, 13(5), 697-706.
[http://dx.doi.org/10.1007/s12551-021-00829-2] [PMID: 34765046]
[49]
Crispino, G.; Di Pasquale, G.; Scimemi, P.; Rodriguez, L.; Galindo Ramirez, F.; De Siati, R.D.; Santarelli, R.M.; Arslan, E.; Bortolozzi, M.; Chiorini, J.A.; Mammano, F. BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice. PLoS One, 2011, 6(8), e23279.
[http://dx.doi.org/10.1371/journal.pone.0023279] [PMID: 21876744]
[50]
Sun, L.; Gao, D.; Chen, J.; Hou, S.; Li, Y.; Huang, Y.; Mammano, F.; Chen, J.; Yang, J. Failure of hearing acquisition in mice with reduced expression of connexin 26 correlates with the abnormal phasing of apoptosis relative to autophagy and defective ATP-dependent Ca2+ signaling in Kölliker’s Organ. Front. Cell. Neurosci., 2022, 16, 816079.
[http://dx.doi.org/10.3389/fncel.2022.816079] [PMID: 35308122]
[51]
Ceriani, F.; Pozzan, T.; Mammano, F. Critical role of ATP-induced ATP release for Ca2+ signaling in nonsensory cell networks of the developing cochlea. Proc. Natl. Acad. Sci. USA, 2016, 113(46), E7194-E7201.
[http://dx.doi.org/10.1073/pnas.1616061113] [PMID: 27807138]
[52]
Johnson, S.L.; Ceriani, F.; Houston, O.; Polishchuk, R.; Polishchuk, E.; Crispino, G.; Zorzi, V.; Mammano, F.; Marcotti, W. Connexin-mediated signaling in nonsensory cells is crucial for the development of sensory inner hair cells in the mouse cochlea. J. Neurosci., 2017, 37(2), 258-268.
[http://dx.doi.org/10.1523/JNEUROSCI.2251-16.2016] [PMID: 28077706]
[53]
Delay, R.J.; Dionne, V.E. Coupling between sensory neurons in the olfactory epithelium. Chem. Senses, 2003, 28(9), 807-815.
[http://dx.doi.org/10.1093/chemse/bjg074] [PMID: 14654449]
[54]
He, Z.; Guo, L.; Shu, Y.; Fang, Q.; Zhou, H.; Liu, Y.; Liu, D.; Lu, L.; Zhang, X.; Ding, X.; Liu, D.; Tang, M.; Kong, W.; Sha, S.; Li, H.; Gao, X.; Chai, R. Autophagy protects auditory hair cells against neomycin-induced damage. Autophagy, 2017, 13(11), 1884-1904.
[http://dx.doi.org/10.1080/15548627.2017.1359449] [PMID: 28968134]
[55]
Liu, W.; Xu, L.; Wang, X.; Zhang, D.; Sun, G.; Wang, M.; Wang, M.; Han, Y.; Chai, R.; Wang, H. PRDX1 activates autophagy via the PTEN-AKT signaling pathway to protect against cisplatin-induced spiral ganglion neuron damage. Autophagy, 2021, 17(12), 4159-4181.
[http://dx.doi.org/10.1080/15548627.2021.1905466] [PMID: 33749526]
[56]
Kühnel, E.; Kleff, V.; Stojanovska, V.; Kaiser, S.; Waldschütz, R.; Herse, F.; Plösch, T.; Winterhager, E.; Gellhaus, A. Placental-specific overexpression of sFlt-1 alters trophoblast differentiation and nutrient transporter expression in an IUGR mouse model. J. Cell. Biochem., 2017, 118(6), 1316-1329.
[http://dx.doi.org/10.1002/jcb.25789] [PMID: 27859593]
[57]
Lin, L.; Wang, Y.F.; Wang, S.Y.; Liu, S.F.; Yu, Z.; Xi, L.; Li, H.W. Ultrastructural pathological changes in the cochlear cells of connexin 26 conditional knockout mice. Mol. Med. Rep., 2013, 8(4), 1029-1036.
[http://dx.doi.org/10.3892/mmr.2013.1614] [PMID: 23917463]
[58]
Lieu, J.E.C.; Kenna, M.; Anne, S.; Davidson, L. Hearing Loss in Children. JAMA, 2020, 324(21), 2195-2205.
[http://dx.doi.org/10.1001/jama.2020.17647] [PMID: 33258894]
[59]
Guomei, C.; Luyan, Z.; Lingling, D.; Chunhong, H.; Shan, C. Concurrent hearing and genetic screening among newborns in Ningbo, China. Comput. Math. Methods Med., 2022, 2022, 1-8.
[http://dx.doi.org/10.1155/2022/1713337] [PMID: 35047053]
[60]
Choi, S.Y.; Lee, K.Y.; Kim, H.J.; Kim, H.K.; Chang, Q.; Park, H.J.; Jeon, C.J.; Lin, X.; Bok, J.; Kim, U.K. Functional evaluation of GJB2 variants in nonsyndromic hearing loss. Mol. Med., 2011, 17(5-6), 550-556.
[http://dx.doi.org/10.2119/molmed.2010.00183] [PMID: 21298213]
[61]
Kamiya, K.; Yum, S.W.; Kurebayashi, N.; Muraki, M.; Ogawa, K.; Karasawa, K.; Miwa, A.; Guo, X.; Gotoh, S.; Sugitani, Y.; Yamanaka, H.; Ito-Kawashima, S.; Iizuka, T.; Sakurai, T.; Noda, T.; Minowa, O.; Ikeda, K. Assembly of the cochlear gap junction macromolecular complex requires connexin 26. J. Clin. Invest., 2014, 124(4), 1598-1607.
[http://dx.doi.org/10.1172/JCI67621] [PMID: 24590285]
[62]
Shi, X.; Qiu, S.; Yan, F.; Shi, L.; Xuan, Y.; Zhuang, W.; Bei, Y.; Yao, H.; Yuan, N.; Yang, S.; Qiao, Y. Polymorphism of the 86th amino acid in CX26 protein and hereditary deafness. J. Otol., 2016, 11(2), 84-87.
[http://dx.doi.org/10.1016/j.joto.2016.05.004] [PMID: 29937815]
[63]
Ahmad, S.; Tang, W.; Chang, Q.; Qu, Y.; Hibshman, J.; Li, Y.; Söhl, G.; Willecke, K.; Chen, P.; Lin, X. Restoration of connexin26 protein level in the cochlea completely rescues hearing in a mouse model of human connexin30-linked deafness. Proc. Natl. Acad. Sci. USA, 2007, 104(4), 1337-1341.
[http://dx.doi.org/10.1073/pnas.0606855104] [PMID: 17227867]
[64]
Xu, K.; Chen, S.; Xie, L.; Qiu, Y.; Liu, X.; Bai, X.; Jin, Y.; Wang, X.; Sun, Y. The protective effects of systemic dexamethasone on sensory epithelial damage and hearing loss in targeted Cx26-null mice. Cell Death Dis., 2022, 13(6), 545.
[http://dx.doi.org/10.1038/s41419-022-04987-3] [PMID: 35688810]
[65]
Shi, Y.; Li, X.; Yang, J. Mutations of CX46/CX50 and cataract development. Front. Mol. Biosci., 2022, 9, 842399.
[http://dx.doi.org/10.3389/fmolb.2022.842399] [PMID: 35223995]
[66]
Banks, E.A.; Toloue, M.M.; Shi, Q.; Zhou, Z.J.; Liu, J.; Nicholson, B.J.; Jiang, J.X. Connexin mutation that causes dominant congenital cataracts inhibits gap junctions, but not hemichannels, in a dominant negative manner. J. Cell Sci., 2009, 122(3), 378-388.
[http://dx.doi.org/10.1242/jcs.034124] [PMID: 19126675]
[67]
Zhou, Y.; Bennett, T.M.; White, T.W.; Shiels, A. Charged multivesicular body protein 4b forms complexes with gap junction proteins during lens fiber cell differentiation. FASEB J., 2023, 37(4), e22801.
[http://dx.doi.org/10.1096/fj.202201368RR] [PMID: 36880430]
[68]
Berthoud, V.M.; Ngezahayo, A. Focus on lens connexins. BMC Cell Biol., 2017, 18(S1)(Suppl. 1), 6.
[http://dx.doi.org/10.1186/s12860-016-0116-6] [PMID: 28124626]
[69]
Shen, J.; Wu, Q.; You, J.; Zhang, X.; Zhu, L.; Xia, X.; Xue, C.; Tian, X. Characterization of a novel gja8 (Cx50) mutation in a new cataract rat model. Invest. Ophthalmol. Vis. Sci., 2023, 64(7), 18.
[http://dx.doi.org/10.1167/iovs.64.7.18] [PMID: 37294706]
[70]
Beyer, E.C.; Berthoud, V.M. Connexin hemichannels in the lens. Front. Physiol., 2014, 5, 20.
[http://dx.doi.org/10.3389/fphys.2014.00020] [PMID: 24575044]
[71]
Minogue, P.J.; Sommer, A.J.; Williams, J.C., Jr; Bledsoe, S.B.; Beyer, E.C.; Berthoud, V.M. Connexin mutants cause cataracts through deposition of apatite. Front. Cell Dev. Biol., 2022, 10, 951231.
[http://dx.doi.org/10.3389/fcell.2022.951231] [PMID: 35938173]
[72]
Berthoud, V.M.; Gao, J.; Minogue, P.J.; Jara, O.; Mathias, R.T.; Beyer, E.C. Connexin mutants compromise the lens circulation and cause cataracts through biomineralization. Int. J. Mol. Sci., 2020, 21(16), 5822.
[http://dx.doi.org/10.3390/ijms21165822] [PMID: 32823750]
[73]
Bennett, T.M.; Zhou, Y.; Meyer, K.J.; Anderson, M.G.; Shiels, A. Whole-exome sequencing prioritizes candidate genes for hereditary cataract in the Emory mouse mutant. G3 (Bethesda), 2023, 13(5), jkad055.
[http://dx.doi.org/10.1093/g3journal/jkad055] [PMID: 36891866]
[74]
Qi, C.; He, Y.; Jiang, C.; Zhang, X.; Zhu, P.; Li, W.; Zhou, H.; Xue, C.; Xia, X. Screening the pathogenic causes of congenital cataract via whole exome sequencing technology in three families: Molecular genetics of congenital cataract. Mol. Med. Rep., 2023, 27(6), 121.
[PMID: 37165913]
[75]
Shiels, A.; Hejtmancik, J.F. Biology of inherited cataracts and opportunities for treatment. Annu. Rev. Vis. Sci., 2019, 5(1), 123-149.
[http://dx.doi.org/10.1146/annurev-vision-091517-034346] [PMID: 31525139]
[76]
Sloan, G.; Selvarajah, D.; Tesfaye, S. Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy. Nat. Rev. Endocrinol., 2021, 17(7), 400-420.
[http://dx.doi.org/10.1038/s41574-021-00496-z] [PMID: 34050323]
[77]
Palumbo, C.; Nicolaci, N.; La Manna, A.A.; Branek, N.; Pissano, M.N. Association between central diabetes insipidus and type 2 diabetes mellitus. Medicina (B. Aires), 2018, 78(2), 127-130. Association between central diabetes insipidus and type 2 diabetes mellitus.
[PMID: 29659364]
[78]
Liu, Y.; Li, M.; Zhang, Z.; Ye, Y.; Zhou, J. Role of microglia-neuron interactions in diabetic encephalopathy. Ageing Res. Rev., 2018, 42, 28-39.
[http://dx.doi.org/10.1016/j.arr.2017.12.005] [PMID: 29247713]
[79]
Simonetto, M.; Infante, M.; Sacco, R.L.; Rundek, T.; Della-Morte, D. A novel anti-inflammatory role of Omega-3 PUFAs in prevention and treatment of atherosclerosis and vascular cognitive impairment and dementia. Nutrients, 2019, 11(10), 2279.
[http://dx.doi.org/10.3390/nu11102279] [PMID: 31547601]
[80]
Quan, M.; Lv, H.; Liu, Z.; Li, K.; Zhang, C.; Shi, L.; Yang, X.; Lei, P.; Zhu, Y.; Ai, D. MST1 suppresses disturbed flow induced atherosclerosis. Circ. Res., 2022, 131(9), 748-764.
[http://dx.doi.org/10.1161/CIRCRESAHA.122.321322] [PMID: 36164986]
[81]
Chen, B.; Yang, L.; Chen, J.; Chen, Y.; Zhang, L.; Wang, L.; Li, X.; Li, Y.; Yu, H. Inhibition of Connexin43 hemichannels with Gap19 protects cerebral ischemia/reperfusion injury via the JAK2/STAT3 pathway in mice. Brain Res. Bull., 2019, 146, 124-135.
[http://dx.doi.org/10.1016/j.brainresbull.2018.12.009] [PMID: 30593877]
[82]
Zhang, W.; Jin, Y.; Wang, D.; Cui, J. Neuroprotective effects of leptin on cerebral ischemia through JAK2/STAT3/PGC-1-mediated mitochondrial function modulation. Brain Res. Bull., 2020, 156, 118-130.
[http://dx.doi.org/10.1016/j.brainresbull.2020.01.002] [PMID: 31935431]
[83]
Rouach, N.; Koulakoff, A.; Abudara, V.; Willecke, K.; Giaume, C. Astroglial metabolic networks sustain hippocampal synaptic transmission. Science, 2008, 322(5907), 1551-1555.
[http://dx.doi.org/10.1126/science.1164022] [PMID: 19056987]
[84]
Egawa, K.; Yamada, J.; Furukawa, T.; Yanagawa, Y.; Fukuda, A. Cl − homeodynamics in gap junction-coupled astrocytic networks on activation of GABAergic synapses. J. Physiol., 2013, 591(16), 3901-3917.
[http://dx.doi.org/10.1113/jphysiol.2013.257162] [PMID: 23732644]
[85]
Jeanson, T.; Pondaven, A.; Ezan, P.; Mouthon, F.; Charvériat, M.; Giaume, C. Antidepressants impact connexin 43 channel functions in astrocytes. Front. Cell. Neurosci., 2016, 9, 495.
[http://dx.doi.org/10.3389/fncel.2015.00495] [PMID: 26778961]
[86]
Jiang, H.; Zhang, Y.; Wang, Z.Z.; Chen, N.H. Connexin 43: An interface connecting neuroinflammation to depression. Molecules, 2023, 28(4), 1820.
[http://dx.doi.org/10.3390/molecules28041820] [PMID: 36838809]
[87]
Quesseveur, G.; Portal, B.; Basile, J.A.; Ezan, P.; Mathou, A.; Halley, H.; Leloup, C.; Fioramonti, X.; Déglon, N.; Giaume, C.; Rampon, C.; Guiard, B.P. Attenuated levels of hippocampal connexin 43 and its phosphorylation correlate with antidepressant- and anxiolytic-like activities in mice. Front. Cell. Neurosci., 2015, 9, 490.
[http://dx.doi.org/10.3389/fncel.2015.00490] [PMID: 26733815]
[88]
Orellana, J.A.; Moraga-Amaro, R.; Díaz-Galarce, R.; Rojas, S.; Maturana, C.J.; Stehberg, J.; Sáez, J.C. Restraint stress increases hemichannel activity in hippocampal glial cells and neurons. Front. Cell. Neurosci., 2015, 9, 102.
[http://dx.doi.org/10.3389/fncel.2015.00102] [PMID: 25883550]
[89]
Trivedi, MH Major depressive disorder in primary care: strategies for identification. J Clin Psychiatry., 2020, 81(2), UT17042BR1C.
[90]
Unützer, J. Diagnosis and treatment of older adults with depression in primary care. Biol. Psychiatry, 2002, 52(3), 285-292.
[http://dx.doi.org/10.1016/S0006-3223(02)01338-0] [PMID: 12182933]
[91]
Bhatt, S.; Devadoss, T.; Manjula, S.N.; Rajangam, J. 5-HT3 receptor antagonism a potential therapeutic approach for the treatment of depression and other disorders. Curr. Neuropharmacol., 2021, 19(9), 1545-1559.
[http://dx.doi.org/10.2174/1570159X18666201015155816] [PMID: 33059577]
[92]
Locke, D.; Bian, S.; Li, H.; Harris, A.L. Post-translational modifications of connexin26 revealed by mass spectrometry. Biochem. J., 2009, 424(3), 385-398.
[http://dx.doi.org/10.1042/BJ20091140] [PMID: 19775242]
[93]
Ratchford, A.M.; Esguerra, C.R.; Moley, K.H. Decreased oocyte-granulosa cell gap junction communication and connexin expression in a type 1 diabetic mouse model. Mol. Endocrinol., 2008, 22(12), 2643-2654.
[http://dx.doi.org/10.1210/me.2007-0495] [PMID: 18829945]
[94]
Zhang, Y.; Wang, X.; Wang, Q.; Ge, H.; Tao, L. Propofol depresses cisplatin cytotoxicity via the inhibition of gap junctions. Mol. Med. Rep., 2016, 13(6), 4715-4720.
[http://dx.doi.org/10.3892/mmr.2016.5119] [PMID: 27082707]
[95]
Huang, D.; Li, C.; Zhang, W.; Qin, J.; Jiang, W.; Hu, C. Dysfunction of astrocytic connexins 30 and 43 in the medial prefrontal cortex and hippocampus mediates depressive-like behaviours. Behav. Brain Res., 2019, 372, 111950.
[http://dx.doi.org/10.1016/j.bbr.2019.111950] [PMID: 31103752]
[96]
Masaki, K. Early disruption of glial communication via connexin gap junction in multiple sclerosis, Baló’s disease and neuromyelitis optica. Neuropathology, 2015, 35(5), 469-480.
[http://dx.doi.org/10.1111/neup.12211] [PMID: 26016402]

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