Research progress on myelinassociated inhibitors and their receptors in spinal cord injury repair

LIU Xin-tong PENG Qing-hua LIU Huai-cun ZHANG Wei-guang

Acta Anatomica Sinica ›› 2024, Vol. 55 ›› Issue (3) : 371-377.

PDF(3494 KB)
Welcome to visit Acta Anatomica Sinica! Today is Chinese
PDF(3494 KB)
Acta Anatomica Sinica ›› 2024, Vol. 55 ›› Issue (3) : 371-377. DOI: 10.16098/j.issn.0529-1356.2024.03.017
Review

Research progress on myelinassociated inhibitors and their receptors in spinal cord injury repair

  • LIU  Xin-tong1  PENG  Qing-hua LIU  Huai-cun2* ZHANG  Wei-guang2*#br#
Author information +
History +

Abstract

Spinal cord injury is a traumatic disease, commonly seen in falling injuries, traffic accidents, heavy injuries, etc, which could cause motor, sensory and autonomic dysfunction below the level of spinal cord injury. Myelin-associated inhibitors play a role in promoting the collapse of growth cones and inhibiting axonal regeneration in the injured spinal cord microenvironment, which is the main reason for the difficult repair of spinal cord injury. Myelinassociated inhibitors (MAIs), such as neurite outgrowth inhibitor (Nogo), oligodendrocyte-myelin glycoprotein (OMgp) and myelin-associated glycoprotein (MAG), along with their receptor proteins, such as Nogo-A/Nogo-66 receptor 1 (NgR1), paired immunoglobulin-like receptor B (PirB), sphingosine-1-phosphate receptor 2 (S1PR2), are the important regulatory factors in the spinal cord microenvironment. They can inhibit therepair process of spinal cord injury by affecting the signaling pathway of neuron axon growth. Although the mechanism of spinal cord injury repair is still unclear, the regulation of myelin-related inhibitory factor proteins and downstream signaling pathways remain an important therapeutic approach for spinal cord injury. In this paper, the role of MAI proteins and their receptors in spinal cord injury repair in recent years were reviewed to provide a new target for spinal cord injury repair and provide more ideas for clinical treatment after spinal cord injury.

Cite this article

Download Citations
LIU Xin-tong PENG Qing-hua LIU Huai-cun ZHANG Wei-guang. Research progress on myelinassociated inhibitors and their receptors in spinal cord injury repair[J]. Acta Anatomica Sinica. 2024, 55(3): 371-377 https://doi.org/10.16098/j.issn.0529-1356.2024.03.017

References

 [1] Anjum A, Yazid M D, Fauzi Daud M, et al. Spinal cord injury: pathophysiology, multimolecular Interactions, and underlying recovery mechanisms[J]. Int J Mol Sci, 2020, 21(20): 1-35.
 [2] Li WX, Li RF, Yu BL. Epidemiological analysis of 956 inpatients with traumatic spinal cord injury from 2012 to 2019[J]. Chinese Journal of Spinal Cord, 2021, 31(7): 626-631. (in Chinese)
李文选, 李瑞峰, 于宝龙. 2012~2019年度956例创伤性脊髓损伤住院患者流行病学分析[J]. 中国脊柱脊髓杂志, 2021, 31(7): 626-631.
 [3] Spinal Cord Injury[EB/OL]. https://www.who.int/news-room/fact-sheets/detail/spinal-cord-injury.
 [4] Egawa N, Lok J, Washida K, et al. Mechanisms of axonal damage and repair after central nervous system injury[J]. Transl Stroke Res, 2017, 8(1): 14-21.
 [5] Ko CC, Tu TH, Wu JC, et al. Acidic fibroblast growth foctor in spinal cord injury[J]. Neurospine, 2019, 16(4):728-738.
 [6] Quraishe S, Forbes L H, Andrews M R. The extracellular environment of the CNS: influence on plasticity, sprouting, and axonal regeneration after spinal cord injury[J]. Neural Plast, 2018, 2018: 2952386.
 [7] Stern S, Hilton BJ, Burnside ER, et al. RhoA drives actin compaction to restrict axon regeneration and astrocyte reactivity after CNS injury[J]. Neuron, 2021, 109(21): 3436-3455.
 [8] Schwab M E. Functions of Nogo proteins and their receptors in the nervous system[J]. Nat Rev Neurosci, 2010, 11(12): 799-811.
 [9] Huber A B, Weinmann O, Brösamle C, et al. Patterns of Nogo mRNA and protein expression in the developing and adult rat and after CNS lesions[J]. J Neurosci, 2002, 22(9): 3553-3567.
 [10] Hu QG, Liu HC, Chen L, et al. Nogo-A protein in rat dorsal root ganglia promotes microtubule polymerization and inflammatory thermal pain sensitization[J]. Acta Anatomica sinica, 2019,50(5): 549-553. (in Chinese)
胡启国, 刘怀存, 陈玲, 等. 大鼠背根神经节中的Nogo-A蛋白促进微管聚合和炎症热痛觉敏化的发生[J]. 解剖学报, 2019, 50(5): 549-553.
 [11] Liu H, Su D, Liu L, et al. Identification of a new functional domain of Nogo-A that promotes inflammatory pain and inhibits neurite growth through binding to NgR1[J]. Faseb J, 2020, 34(8): 10948-10965.
 [12] Mohammed R, Opara K, Lall R, et al. Evaluating the effectiveness of anti-Nogo treatment in spinal cord injuries[J]. Neural Dev, 2020, 15(1): 1-9.
 [13] Kucher K, Johns D, Maier D, et al. First-in-man intrathecal application of neurite growth-promoting anti-Nogo-A antibodies in acute spinal cord injury[J]. Neurorehabil Neural Repair, 2018, 32(6-7): 578-589.
 [14] Drake S, Fournier A. Nogo BACE jumps on the exosome[J]. J Biol Chem, 2020, 295(8): 2184-2185.
 [15] Sekine Y, Lindborg JA, Strittmatter S M. A proteolytic C-terminal fragment of Nogo-A (reticulon-4A) is released in exosomes and potently inhibits axon regeneration[J]. J Biol Chem, 2020, 295(8): 2175-2183.
 [16] Zuo Y, Sun H, Song L, et al. LncRNA FTX involves in the Nogo-66-induced inhibition of neurite outgrowth through regulating PDK1/PKB/GSK-3βpathway[J]. Cell Mol Neurobiol, 2020, 40(7): 1143-1153.
 [17] Roy A, Pathak Z, Kumar H. Strategies to neutralize RhoA/ROCK pathway after spinal cord injury[J]. Exp Neurol, 2021, 343: 113794.
 [18] Fan YJ, Li L, Xu J, et al. The role of different OMgp domains in inhibiting neurite growth[J]. Chinese Journal of Cell Biology, 2004, 26(3): 290-296. (in Chinese)
樊拥军, 李龙, 许健,等. OMgp不同结构域在抑制神经突起生长中的作用[J]. 细胞生物学杂志, 2004, 26(3): 290-296.
 [19] Dou F, Huang L, Yu P, et al. Temporospatial expression and cellular localization of oligodendrocyte myelin glycoprotein (OMgp) after traumatic spinal cord injury in adult rats[J]. J Neurotrauma, 2009, 26(12): 2299-2311.
 [20] Ji B, Case LC, Liu K, et al. Assessment of functional recovery and axonal sprouting in oligodendrocyte-myelin glycoprotein (OMgp) null mice after spinal cord injury[J]. Mol Cell Neurosci, 2008, 39(2): 258-267.
 [21] Zearfoss NR, Johnson ES, Ryder SP. hnRNP A1 and secondary structure coordinate alternative splicing of Mag[J]. Rna, 2013, 19(7): 948-957.
 [22] Quarles RH. Myelin-associated glycoprotein (MAG): past, present and beyond[J]. J Neurochem, 2007, 100(6): 1431-1448.
 [23] Cafferty WB, Duffy P, Huebner E, et al. MAG and OMgp synergize with Nogo-A to restrict axonal growth and neurological recovery after spinal cord trauma[J]. J Neurosci, 2010, 30(20): 6825-6837.
 [24] Li M, Shibata A, Li C, et al. Myelin-associated glycoprotein inhibits neurite/axon growth and causes growth cone collapse[J]. J Neurosci Res, 1996, 46(4): 404-414.
[25] Lee J K, Geoffroy CG, Chan AF, et al. Assessing spinal axon regeneration and sprouting in Nogo, MAG, and OMgp-Deficient Mice[J]. Neuron, 2010, 66(5): 663-670.
[26] Zhang A, Bai Z, Yi W, et al. Overexpression of miR-338-5p in exosomes derived from mesenchymal stromal cells provides neuroprotective effects by the Cnr1/Rap1/Akt pathway after spinal cord injury in rats[J]. Neurosci Lett, 2021, 761: 1-12.
 [27] Buzoianu-Anguiano V, Estrada IJ. Paraplegia: Strategies to Repair Spinal Cord Injuries: Single vs Combined Treatments[M]. London: IntechOpen, 2020: 1-18.
[28] Wang X, Zhou T, Maynard GD, et al. Nogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury[J]. Brain, 2020, 143(6): 1697-1713.
 [29] Mi S, Lee X, Shao Z, et al. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex[J]. Nat Neurosci, 2004, 7(3): 221-228.
 [30] Park JB, Yiu G, Kaneko S, et al. A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors[J]. Neuron, 2005, 45(3): 345-351.
 [31] Ito S, Nagoshi N, Tsuji O, et al. LOTUS inhibits neuronal apoptosis and promotes tract regeneration in contusive spinal cord injury model mice[J]. eNeuro, 2018, 5(5): ENEURO.0303-18.2018.
 [32] Lv B, Yuan W, Xu S, et al. Lentivirus-siNgR199 promotes axonal regeneration and functional recovery in rats[J]. Int J Neurosci, 2012, 122(3): 133-139.
 [33] Xu J, He J, He H, et al. Comparison of RNAi NgR and NEP1-40 in acting on axonal regeneration after spinal cord injury in rat models[J]. Mol Neurobiol, 2017, 54(10): 8321-8331.
 [34] Wang YT, Lu XM, Zhu F, et al. Ameliorative effects of p75NTR-ED-Fc on axonal regeneration and functional recovery in spinal cord-injured rats[J]. Mol Neurobiol, 2015, 52(3): 1821-1834.
 [35] Wu H, Ding L, Wang Y, et al. MiR-615 regulates NSC differentiation in vitro and contributes to spinal cord injury repair by targeting LINGO-1[J]. Mol Neurobiol, 2020, 57(7): 3057-3074.
 [36] Mi S, Pepinsky RB, Cadavid D. Blocking LINGO-1 as a therapy to promote CNS repair: from concept to the clinic[J]. CNS Drugs, 2013, 27(7): 493-503.
 [37] Vaccaro G, Dumoulin A, Zuñiga NR, et al. The Nogo-66 receptors NgR1 and NgR3 are required for commissural axon pathfinding[J]. J Neurosci, 2022, 42(20): 4087-4100.
[38] Takai T. Paired immunoglobulin-like receptors and their MHC class I recognition[J]. Immunology, 2005, 115(4): 433-440.
 [39] Liu J, Wang Y, Fu W. Axon regeneration impediment: the role of paired immunoglobulin-like receptor B[J]. Neural Regen Res, 2015, 10(8): 1338-1342.
 [40] Liu J, Mi YJ, Jiang FL. Research progress in the treatment of central nervous system regeneration with PirB as target [J]. Journal of Neuroanatomy, 2014, 30(3): 372-376. (in Chinese)
刘洁, 米亚静, 姜凤良. 以PirB为靶点治疗中枢神经再生的研究进展[J]. 神经解剖学杂志, 2014, 30(3): 372-376.
 [41] Bombeiro AL, Thomé R, Oliveira Nunes SL, et al. MHC-I and PirB upregulation in the central and peripheral nervous system following sciatic nerve injury[J]. PLoS One, 2016, 11(8): 1-18.
 [42] Wang J, Zhang Y, Xia J, et al. Neuronal PirB upregulated in cerebral ischemia acts as an attractive theranostic target for ischemic stroke[J]. J Am Heart Assoc, 2018, 7(3): 1-13.
 [43] Lu XM, Mao M, Xiao L, et al. Nucleic acid vaccine targeting Nogo-66 receptor and paired immunoglobulin-like receptor B as an immunotherapy strategy for spinal cord injury in rats[J]. Neurotherapeutics, 2019, 16(2): 381-393.
 [44] Fujita Y, Takashima R, Endo S, et al. The p75 receptor mediates axon growth inhibition through an association with PIR-B[J]. Cell Death Dis, 2011, 2(9): 1-7.
 [45] Kurihara Y, Takai T, Takei K. Nogo receptor antagonist LOTUS exerts suppression on axonal growthinhibiting receptor PIR-B[J]. J Neurochem, 2020, 155(3): 285-299.
 [46] Ren R, Pang B, Han Y, et al. A glimpse of the structural biology of the metabolism of sphingosine-1-phosphate[J]. Contact, 2021, 4: 1-22.
 [47] Yu L, He L, Gan B, et al. Structural insights into sphingosine-1-phosphate receptor activation[J]. Proc Natl Acad Sci USA, 2022, 119(16): 1-9.
 [48] Kempf A, Tews B, Arzt ME, et al. The sphingolipid receptor S1PR2 is a receptor for Nogo-a repressing synaptic plasticity[J]. PLoS Biol, 2014, 12(1): 1-16.
 [49] Seyedsadr MS, Weinmann O, Amorim A, et al. Inactivation of sphingosine1-phosphate receptor 2 (S1PR2) decreases demyelination and enhances remyelination in animal models of multiple sclerosis[J]. Neurobiol Dis, 2019, 124: 189-201.

Funding

Youth Fund of the National Natural Science Foundation of China
PDF(3494 KB)

Accesses

Citation

Detail

Sections
Recommended

/