-
外周神经系统(PNS)是中枢神经系统发出,导向人体各部分的神经,也称周围神经系统。外周神经的主要成分是神经纤维,包括传入神经纤维和传出神经纤维。外周神经损伤约占所有创伤的2.8%[1],可导致患者的感觉与运动功能发生障碍。外周神经损伤后机体自身有一定的再生能力但修复速度很慢,因此,借助药物途径促进外周神经再生修复是临床治疗的关键[2-3]。了解与外周神经再生相关的信号通路,有助于外周神经损伤后修复药物的研发。
Signal pathways related to regeneration after peripheral nerve injury
-
摘要: 由于神经元损伤后的自身再修复能力有限,临床上对于神经损伤一直缺乏有效的治疗手段,因此,寻找促进神经损伤后修复的药物,以及探索其相关作用机制始终是神经科学领域的研究热点。有研究表明,在外周神经组织中,神经元细胞和雪旺细胞内的信号通路对于外周神经损伤后再生有着重要作用。本文综述了雪旺细胞和神经元内与外周神经再生相关的信号通路以及与外周神经损伤相关的疾病,为进一步探索外周神经损伤后再生机制提供依据。Abstract: Due to the limited self-repair ability of neurons after injury, there has been a lack of effective treatments for nerve injury in clinical practice. So, to find drugs that promote the repair after nerve injury has become a research hotspot. Schwann cells and neurons play an important role in regeneration of the peripheral nerves after injury. This review summarizes the classification of peripheral nerve injury, the signaling pathways related to peripheral nerve regeneration in Schwann cells and neurons as well as diseases related to peripheral nerve injury, and provides a basis for further exploration of the regeneration mechanism after peripheral nerve injury.
-
Key words:
- peripheral nerve injury /
- regeneration /
- Schwann cell /
- neuron /
- signal pathway
-
[1] MA F K, XIAO Z F, CHEN B, et al. Linear ordered collagen scaffolds loaded with collagen-binding basic fibroblast growth factor facilitate recovery of sciatic nerve injury in rats[J]. Tissue Eng Part A,2014,20(7-8):1253-1262. doi: 10.1089/ten.tea.2013.0158 [2] HÖKE A. A (heat) shock to the system promotes peripheral nerve regeneration[J]. J Clin Invest,2011,121(11):4231-4234. doi: 10.1172/JCI59320 [3] AMNIATTALAB A, MOHAMMADI R. Functional, histopathological and immunohistichemical assessments of cyclosporine A on sciatic nerve regeneration using allografts: a rat sciatic nerve model[J]. Bull Emerg Trauma,2017,5(3):152-159. [4] LV J, SUN X L, MA J X, et al. Netrin-1 induces the migration of Schwann cells via p38 MAPK and PI3K-Akt signaling pathway mediated by the UNC5B receptor[J]. Biochem Biophys Res Commun,2015,464(1):263-268. doi: 10.1016/j.bbrc.2015.06.140 [5] DOMÈNECH-ESTÉVEZ E, BALOUI H, MENG X S, et al. Akt regulates axon wrapping and myelin sheath thickness in the PNS[J]. J Neurosci,2016,36(16):4506-4521. doi: 10.1523/JNEUROSCI.3521-15.2016 [6] HE B, LIU S Q, CHEN Q, et al. Carboxymethylated chitosan stimulates proliferation of Schwann cells in vitro via the activation of the ERK and Akt signaling pathways[J]. Eur J Pharmacol,2011,667(1-3):195-201. doi: 10.1016/j.ejphar.2011.06.001 [7] CHRAST R, SAHER G, NAVE K A, et al. Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models[J]. J Lipid Res,2011,52(3):419-434. doi: 10.1194/jlr.R009761 [8] LEWIS C A, GRIFFITHS B, SANTOS C R, et al. Regulation of the SREBP transcription factors by mTORC1[J]. Biochem Soc Trans,2011,39(2):495-499. doi: 10.1042/BST0390495 [9] CARON A, RICHARD D, LAPLANTE M. The roles of mTOR complexes in lipid metabolism[J]. Annu Rev Nutr,2015,35:321-348. doi: 10.1146/annurev-nutr-071714-034355 [10] TOPISIROVIC I, SONENBERG N. mRNA translation and energy metabolism in cancer: the role of the MAPK and mTORC1 pathways[J]. Cold Spring Harb Symp Quant Biol,2011,76:355-367. doi: 10.1101/sqb.2011.76.010785 [11] AGTHONG S, KAEWSEMA A, TANOMSRIDEJCHAI N, et al. Activation of MAPK ERK in peripheral nerve after injury[J]. BMC Neurosci,2006,7:45. doi: 10.1186/1471-2202-7-45 [12] KAO S C, WU H, XIE J M, et al. Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation[J]. Science,2009,323(5914):651-654. doi: 10.1126/science.1166562 [13] LEMKE G. Neuregulins in development[J]. Mol Cell Neurosci,1996,7(4):247-262. doi: 10.1006/mcne.1996.0019 [14] MEI L, XIONG W C. Neuregulin 1 in neural development, synaptic plasticity and schizophrenia[J]. Nat Rev Neurosci,2008,9(6):437-452. doi: 10.1038/nrn2392 [15] SCHLOSSHAUER B, MÜLLER E, SCHRÖDER B, et al. Rat Schwann cells in bioresorbable nerve guides to promote and accelerate axonal regeneration[J]. Brain Res,2003,963(1-2):321-326. doi: 10.1016/S0006-8993(02)03930-6 [16] TSENG C Y, HU G L, AMBRON R T, et al. Histologic analysis of Schwann cell migration and peripheral nerve regeneration in the autogenous venous nerve conduit (AVNC)[J]. J Reconstr Microsurg,2003,19(5):331-340. doi: 10.1055/s-2003-42502 [17] LEBLANC S E, SRINIVASAN R, FERRI C, et al. Regulation of cholesterol/lipid biosynthetic genes by Egr2/Krox20 during peripheral nerve myelination[J]. J Neurochem,2005,93(3):737-748. doi: 10.1111/j.1471-4159.2005.03056.x [18] NUSSE R. WNT targets. Repression and activation[J]. Trends Genet,1999,15(1):1-3. doi: 10.1016/S0168-9525(98)01634-5 [19] ZHOU X, ZHAN Z Y, TANG C G, et al. Silencing Celsr2 inhibits the proliferation and migration of Schwann cells through suppressing the Wnt/β-catenin signaling pathway[J]. Biochem Biophys Res Commun,2020,533(4):623-630. doi: 10.1016/j.bbrc.2020.09.015 [20] YU J, WANG S J, WU C, et al. Deep sequencing reveals the significant involvement of cAMP-related signaling pathways following sciatic nerve crush[J]. Neurochem Res,2017,42(12):3603-3611. doi: 10.1007/s11064-017-2409-3 [21] FERNANDES K A, HARDER J M, FORNAROLA L B, et al. JNK2 and JNK3 are major regulators of axonal injury-induced retinal ganglion cell death[J]. Neurobiol Dis,2012,46(2):393-401. doi: 10.1016/j.nbd.2012.02.003 [22] NIX P, HISAMOTO N, MATSUMOTO K, et al. Axon regeneration requires coordinate activation of p38 and JNK MAPK pathways[J]. Proc Natl Acad Sci USA,2011,108(26):10738-10743. doi: 10.1073/pnas.1104830108 [23] SIMON D J, PITTS J, HERTZ N T, et al. Axon degeneration gated by retrograde activation of somatic pro-apoptotic signaling[J]. Cell,2016,164(5):1031-1045. doi: 10.1016/j.cell.2016.01.032 [24] YAMAUCHI K, OSUKA K, TAKAYASU M, et al. Activation of JAK/STAT signalling in neurons following spinal cord injury in mice[J]. J Neurochem,2006,96(4):1060-1070. doi: 10.1111/j.1471-4159.2005.03559.x [25] MOLET J, MAUBORGNE A, DIALLO M, et al. Microglial Janus kinase/signal transduction and activator of transcription 3 pathway activity directly impacts astrocyte and spinal neuron characteristics[J]. J Neurochem,2016,136(1):133-147. doi: 10.1111/jnc.13375 [26] QIU J, CAFFERTY W B, MCMAHON S B, et al. Conditioning injury-induced spinal axon regeneration requires signal transducer and activator of transcription 3 activation[J]. J Neurosci,2005,25(7):1645-1653. doi: 10.1523/JNEUROSCI.3269-04.2005 [27] HUR E M, SAIJILAFU, LEE B D, et al. GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules[J]. Genes Dev,2011,25(18):1968-1981. doi: 10.1101/gad.17015911 [28] HUR E M, SAIJILAFU, ZHOU F Q. Growing the growth cone: remodeling the cytoskeleton to promote axon regeneration[J]. Trends Neurosci,2012,35(3):164-174. doi: 10.1016/j.tins.2011.11.002 [29] EBENEZER G J, O'DONNELL R, HAUER P, et al. Impaired neurovascular repair in subjects with diabetes following experimental intracutaneous axotomy[J]. Brain,2011,134(Pt 6):1853-1863. [30] WANG L, CHOPP M, SZALAD A, et al. Thymosin β4 promotes the recovery of peripheral neuropathy in type II diabetic mice[J]. Neurobiol Dis,2012,48(3):546-555. doi: 10.1016/j.nbd.2012.08.002