Role of collapsin response mediator proteins in optic nerve injury

doi:10.16352/j.issn.1001-6325.2025.01.0102

Abstract

Abstract: Collapsin response mediator proteins (CRMPs), also known as dihydropyrimidine-like proteins, contain five isoforms (CRMP1, CRMP2, CRMP3, CRMP4, CRMP5). In central nervous system, CRMPs are mainly involved in a variety of physiological processes such as neuronal differentiation and migration, synaptic plasticity, neurite growth and development and guiding extension. Recent studies have found that inhibiting or reducing the phosphorylation of CRMPs can affect the survival and axonal regeneration of retinal ganglion cells (RGCs) after optic nerve injury, which may provide new ideas for the treatment of optic nerve injury in the future.

Key words: collapsin response mediator proteins, optic nerve injury, retinal ganglion cell, axonal regeneration

CLC Number:

ZHU Yuchun, XI Xinyuan, YANG Zhen, FENG Dongfu. Role of collapsin response mediator proteins in optic nerve injury[J]. Basic & Clinical Medicine, 2025, 45(1): 102-106.

References

[1] Li CP, Wu S, Sun YQ, et al. Lhx2 promotes axon regeneration of adult retinal ganglion cells and rescues neurodegeneration in mouse models of glaucoma[J]. Cell Rep Med, 2024,5:101554.doi: 10.1016/j.xcrm.2024.101554.
[2] Kawashima T, Jitsuki-Takahashi A, Takizawa K, et al. Phosphorylation of collapsin response mediator protein 1 (CRMP1) at tyrosine 504 residue regulates semaphorin 3A-induced cortical dendritic growth[J]. J Neurochem,2021,157:1207-1221.
[3] Tsai YC, Huang SM, Peng HH, et al. Imbalance of synaptic and extrasynaptic NMDA receptors induced by the deletion of CRMP1 accelerates age-related cognitive decline in mice[J]. Neurobiol Aging, 2024,135:48-59.
[4] Sugeno A, Piao W, Yamazaki M, et al. Cortical transcriptome analysis after spinal cord injury reveals the regenerative mechanism of central nervous system in CRMP2 knock-in mice[J]. Neural Regen Res, 2021,16:1258-1265.
[5] Grycel K, Larsen NY, Feng Y, et al. CRMP2 conditional knockout changes axonal function and ultrastructure of axons in mice corpus callosum[J]. Mol Cell Neurosci, 2023,126:103882. doi: 10.1016/j.mcn.2023.103882.
[6] Ji ZS, Li JP, Fu CH, et al. Spastin interacts with collapsin response mediator protein 3 to regulate neurite growth and branching[J]. Neural Regen Res, 2021,16:2549-2556.
[7] Sun YY, Zhu L, Sun ZL, et al. CRMP2 improves memory deficits by enhancing the maturation of neuronal dendritic spines after traumatic brain injury[J]. Exp Neurol,2020,328:113253.doi: 10.1016/j.expneurol.2020.113253.
[8] Xu K, Wang D, He Y, et al. Identification of anti-collapsin response mediator protein 2 antibodies in patients with encephalitis or encephalomyelitis[J]. Front Immunol, 2022,13:854445. doi: 10.3389/fimmu.2022.854445.
[9] Maimon R, Ankol L, Gradus Pery T, et al. A CRMP4-dependent retrograde axon-to-soma death signal in amyotrophic lateral sclerosis[J]. EMBO J, 2021,40:e107586. doi: 10.15252/embj.2020107586.
[10] Lukomska A, Theune WC, Xing J, et al. Experimental gene expression of developmentally downregulated Crmp1, Crmp4, and Crmp5 promotes axon regeneration and retinal ganglion cell survival after optic nerve injury[J].Brain Res,2023,1809:148368.doi: 10.1016/j.brainres.2023.148368.
[11] Zhang JN, Michel U, Lenz C, et al.Calpain-mediated cleavage of collapsin response mediator protein-2 drives acute axonal degeneration[J]. Sci Rep,2016,6:37050.doi: 10.1038/srep37050.
[12] Alexandris AS, Lee Y, Lehar M, et al. Traumatic axonal injury in the optic nerve: the selective role of SARM1 in the evolution of distal axonopathy[J]. J Neurotrauma,2023,40:1743-1761.
[13] Kinoshita Y, Kondo S, Takahashi K, et al. Genetic inhibition of CRMP2 phosphorylation delays Wallerian degeneration after optic nerve injury[J]. Biochem Biophys Res Commun,2019,514:1037-1039.
[14] Chen X, Yuan R, Gao L, et al. Induction of CRMP-2 phosphorylation by CDK5 restricts the repair of damaged optic nerve[J]. J Cell Physiol,2019,234:11240-11246.
[15] Leibinger M, Andreadaki A, Golla R, et al. Boosting CNS axon regeneration by harnessing antagonistic effects of GSK3 activity[J]. Proc Natl Acad Sci U S A,2017,114:E5454-E5463.
[16] Chiha W, Bartlett CA, Petratos S, et al.Intravitreal application of AAV-BDNF or mutant AAV-CRMP2 protects retinal ganglion cells and stabilizes axons and myelin after partial optic nerveinjury[J].Exp Neurol,2020,326:113167.doi: 10.1016/j.expneurol.2019.113167.
[17] Kondo S, Takahashi K, Kinoshita Y, et al. Genetic inhibition of CRMP2 phosphorylation at serine 522 promotes axonal regeneration after optic nerve injury[J]. Sci Rep,2019,9:7188.doi: 10.1038/s41598-019-43658-w.
[18] Brahma MM, Takahashi K, Namekata K, et al. Genetic inhibition of collapsin response mediator protein-2 phosphorylation ameliorates retinal ganglion cell death in normal-tension glaucoma models[J]. Genes Cells,2022,27:526-536.
[19] Lauzi J, Anders F, Liu H, et al. Neuroprotective and neuroregenerative effects of CRMP-5 on retinal ganglion cells in an experimental in vivo and in vitro model of glaucoma[J].PLoS One,2019,14:e0207190.doi: 10.1371/journal.pone.0207190.
[20] Wang Y, Wang XL, Xie GL, et al. Collapsin response mediator protein-2-induced retinal ischemic injury in a novel mice model of ocular ischemia syndrome[J]. Chin Med J (Engl),2017,130:1342-1351.
[21] Han P, She Y, Yang Z, et al. Cbln1 regulates axon growth and guidance in multiple neural regions[J].PLoS Biol,2022,20:e3001853.doi: 10.1371/journal.pbio.3001853.
[22] Schneider F, Metz I, Rust MB. Regulation of actin filament assembly and disassembly in growth cone motility and axon guidance[J]. Brain Res Bull,2023,192:21-35.
[23] Liu ZZ, Zhu J, Wang CL, et al. CRMP2 and CRMP4 are differentially required for axon guidance and growth in zebrafish retinal neurons[J]. Neural Plast,2018,2018:8791304.doi: 10.1155/2018/8791304.
[24] Nishijima E, Namekata K, Kimura A, et al. Topical ripasudil stimulates neuroprotection and axon regeneration in adult mice following optic nerve injury[J]. Sci Rep,2020,10:15709.doi: 10.1038/s41598-020-72748-3.
[25] Wang Y, Brahma MM, Takahashi K,et al. Drug treatment attenuates retinal ganglion cell death by inhibit-ing collapsin response mediator protein 2 phosphorylation in mouse models of normal tension glaucoma[J]. Neuromolecular Med, 2024,26:13.doi: 10.1007/s12017-024-08778-1.