硫酸软骨素蛋白多糖在脊髓损伤中的研究进展

刘永, 史永强, 毛鹏, 张海鸿

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重庆医科大学学报 ›› 2024, Vol. 49 ›› Issue (03) : 231-236. DOI: 10.13406/j.cnki.cyxb.003444
综述

硫酸软骨素蛋白多糖在脊髓损伤中的研究进展

作者信息 +

Research progress of chondroitin sulfate proteoglycans in spinal cord injury

Author information +
History +

摘要

硫酸软骨素蛋白多糖(chondroitin sulfate proteoglycans,CSPGs)是中枢神经系统细胞外基质的组成部分,在中枢神经系统发育、正常维持及病理过程中都发挥着关键的作用。脊髓损伤后,损伤部位CSPGs的表达明显上调,这主要源于病变部位活化的星形胶质细胞。CSPGs的上调会限制脊髓损伤部位的轴突再生、传导和再髓鞘化,并且可以促进脊髓损伤中的炎症反应,不利于脊髓损伤后神经功能恢复。因此,抑制CSPGs可能是促进脊髓损伤后轴突再生和功能恢复的有效治疗方法。本文对CSPGs在脊髓损伤中的研究现状进行综述。

Abstract

Chondroitin sulfate proteoglycans(CSPGs) are components of the extracellular matrix of the central nervous system,and play key roles in the development,function maintenance,and pathological process of the central nervous system. After spinal cord injury,the expression of CSPGs at the injury site is significantly upregulated,which is mainly due to activated astrocytes at the lesion site. Upregulation of CSPGs can restrict axon regeneration,conduction,and re-myelination at the site of spinal cord injury,and can promote the inflammatory response in spinal cord injury,which impedes the recovery of nerve function after spinal cord injury. Therefore,inhibition of CSPGs may be an effective treatment to promote axonal regeneration and functional recovery after spinal cord injury. This study reviews the current status of research on CSPGs in spinal cord injury.

关键词

硫酸软骨素蛋白多糖 / 脊髓损伤 / 糖胺聚糖 / 神经修复

Key words

chondroitin sulfate proteoglycan / spinal cord injury / glycosaminoglycan / nerve repair

中图分类号

R651.2

引用本文

导出引用
刘永 , 史永强 , 毛鹏 , . 硫酸软骨素蛋白多糖在脊髓损伤中的研究进展. 重庆医科大学学报. 2024, 49(03): 231-236 https://doi.org/10.13406/j.cnki.cyxb.003444
Liu Yong, Shi Yongqiang, Mao Peng, et al. Research progress of chondroitin sulfate proteoglycans in spinal cord injury[J]. Journal of Chongqing Medical University. 2024, 49(03): 231-236 https://doi.org/10.13406/j.cnki.cyxb.003444

参考文献

1
Bieler L Vogl M Kirchinger M,et al. The prenylflavonoid ENDF1 overrules central nervous system growth inhibitors and facilitates regeneration of DRG neurons[J]. Front Cell Neurosci201913:332.
2
Guest J Datta N Jimsheleishvili G,et al. Pathophysiology,classification and comorbidities after traumatic spinal cord injury[J]. J Pers Med202212(7):1126.
3
Anderson MA Burda JE Ren YL,et al. Astrocyte scar formation aids central nervous system axon regeneration[J]. Nature2016532(7598):195-200.
4
Chambel SS Cruz CD. Axonal growth inhibitors and their receptors in spinal cord injury:from biology to clinical translation[J]. Neural Regen Res202318(12):2573-2581.
5
Alizadeh A Dyck SM Karimi-Abdolrezaee S. Traumatic spinal cord injury:an overview of pathophysiology,models and acute injury mechanisms[J]. Front Neurol201910:282.
6
Adams KL Gallo V. The diversity and disparity of the glial scar[J]. Nat Neurosci201821(1):9-15.
7
Mukherjee N Nandi S Garg S,et al. Targeting chondroitin sulfate proteoglycans:an emerging therapeutic strategy to treat CNS injury[J]. ACS Chem Neurosci202011(3):231-232.
8
Stephenson EL Yong VW. Pro-inflammatory roles of chondroitin sulfate proteoglycans in disorders of the central nervous system[J]. Matrix Biol201871/72:432-442.
9
Dyck SM Karimi-Abdolrezaee S. Chondroitin sulfate proteoglycans:key modulators in the developing and pathologic central nervous system[J]. Exp Neurol2015269:169-187.
10
Viapiano MS Matthews RT. From barriers to bridges:chondroitin sulfate proteoglycans in neuropathology[J]. Trends Mol Med200612(10):488-496.
11
Morawski M Brückner G Arendt T,et al. Aggrecan:beyond cartilage and into the brain[J]. Int J Biochem Cell Biol201244(5):690-693.
12
Frischknecht R Seidenbecher CI. Brevican:a key proteoglycan in the perisynaptic extracellular matrix of the brain[J]. Int J Biochem Cell Biol201244(7):1051-1054.
13
Schmidt S Arendt T Morawski M,et al. Neurocan contributes to perineuronal net development[J]. Neuroscience2020442:69-86.
14
Islam S Watanabe H. Versican:a dynamic regulator of the extracellular matrix[J]. J Histochem Cytochem202068(11):763-775.
15
Hesp ZC Yoseph RY Suzuki R,et al. Proliferating NG2-cell-dependent angiogenesis and scar formation alter axon growth and functional recovery after spinal cord injury in mice[J]. J Neurosci201838(6):1366-1382.
16
Kolb J Tsata V John N,et al. Small leucine-rich proteoglycans inhibit CNS regeneration by modifying the structural and mechanical properties of the lesion environment[J]. Nat Commun202314(1):6814.
17
Sherman LS Back SA. A ‘GAG’ reflex prevents repair of the damaged CNS[J]. Trends Neurosci200831(1):44-52.
18
Susarla BT Laing ED Yu PP,et al. Smad proteins differentially regulate transforming growth factor-β-mediated induction of chondroitin sulfate proteoglycans[J]. J Neurochem2011119(4):868-878.
19
Sorg BA Berretta S Blacktop JM,et al. Casting a wide net:role of perineuronal nets in neural plasticity[J]. J Neurosci201636(45):11459-11468.
20
Beurdeley M Spatazza J Lee HH,et al. Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex[J]. J Neurosci201232(27):9429-9437.
21
Foscarin S Raha-Chowdhury R Fawcett JW,et al. Brain ageing changes proteoglycan sulfation,rendering perineuronal nets more inhibitory[J]. Aging20179(6):1607-1622.
22
Coles CH Shen YJ Tenney AP,et al. Proteoglycan-specific molecular switch for RPTPσ clustering and neuronal extension[J]. Science2011332(6028):484-488.
23
Maeda N. Proteoglycans and neuronal migration in the cerebral cortex during development and disease[J]. Front Neurosci20159:98.
24
Geissler M Gottschling C Aguado A,et al. Primary hippocampal neurons,which lack four crucial extracellular matrix molecules,display abnormalities of synaptic structure and function and severe deficits in perineuronal net formation[J]. J Neurosci201333(18):7742-7755.
25
Barros CS Franco SJ Müller U. Extracellular matrix:functions in the nervous system[J]. Cold Spring Harb Perspect Biol20113(1):a005108.
26
Snow DM Lemmon V Carrino DA,et al. Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro [J]. Exp Neurol1990109(1):111-130.
27
Pendleton JC Shamblott MJ Gary DS,et al. Chondroitin sulfate proteoglycans inhibit oligodendrocyte myelination through PTPσ[J]. Exp Neurol2013247:113-121.
28
Morawski M Brückner G Jäger C,et al. Involvement of perineuronal and perisynaptic extracellular matrix in Alzheimer’s disease neuropathology[J]. Brain Pathol201222(4):547-561.
29
Yang S Hilton S Alves JN,et al. Antibody recognizing 4-sulfated chondroitin sulfate proteoglycans restores memory in tauopathy-induced neurodegeneration[J]. Neurobiol Aging201759:197-209.
30
Yang X. Chondroitin sulfate proteoglycans:key modulators of neuronal plasticity,long-term memory,neurodegenerative,and psychiatric disorders[J]. Rev Neurosci202031(5):555-568.
31
Feliu A Mestre L Carrillo-Salinas FJ,et al. 2-arachidonoylglycerol reduces chondroitin sulphate proteoglycan production by astrocytes and enhances oligodendrocyte differentiation under inhibitory conditions[J]. Glia202068(6):1255-1273.
32
Mukhamedshina YO Povysheva TV Nikolenko VN,et al. Upregulation of proteoglycans in the perilesion perimeter in ventral horns after spinal cord injury[J]. Neurosci Lett2019704:220-228.
33
Buss A Pech K Kakulas BA,et al. NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury[J]. BMC Neurol20099:32.
34
Zhang C Kang JN Zhang XD,et al. Spatiotemporal dynamics of the cellular components involved in glial scar formation following spinal cord injury[J]. Biomedecine Pharmacother2022153:113500.
35
Tamaru T Kobayakawa K Saiwai H,et al. Glial scar survives until the chronic phase by recruiting scar-forming astrocytes after spinal cord injury[J]. Exp Neurol2023359:114264.
36
Hara M Kobayakawa K Ohkawa Y,et al. Interaction of reactive astrocytes with type I collagen induces astrocytic scar formation through the integrin-N-cadherin pathway after spinal cord injury[J]. Nat Med201723(7):818-828.
37
Schachtrup C Ryu JK Helmrick MJ,et al. Fibrinogen triggers astrocyte scar formation by promoting the availability of active TGF-beta after vascular damage[J]. J Neurosci201030(17):5843-5854.
38
Jahan N Hannila SS. Transforming growth factor β-induced expression of chondroitin sulfate proteoglycans is mediated through non-Smad signaling pathways[J]. Exp Neurol2015263:372-384.
39
Petrosyan HA Hunanyan AS Alessi V,et al. Neutralization of inhibitory molecule NG2 improves synaptic transmission,retrograde transport,and locomotor function after spinal cord injury in adult rats[J]. J Neurosci201333(9):4032-4043.
40
Dyck S Kataria H Akbari-Kelachayeh K,et al. LAR and PTPσ receptors are negative regulators of oligodendrogenesis and oligodendrocyte integrity in spinal cord injury[J]. Glia201967(1):125-145.
41
Karus M Ulc A Ehrlich M,et al. Regulation of oligodendrocyte precursor maintenance by chondroitin sulphate glycosaminoglycans[J]. Glia201664(2):270-286.
42
Dyck S Kataria H Alizadeh A,et al. Perturbing chondroitin sulfate proteoglycan signaling through LAR and PTPσ receptors promotes a beneficial inflammatory response following spinal cord injury[J]. J Neuroinflammation201815(1):90.
43
Rolls A Shechter R London A,et al. Two faces of chondroitin sulfate proteoglycan in spinal cord repair:a role in microglia/macrophage activation[J]. PLoS Med20085(8):e171.
44
Francos-Quijorna I Sánchez-Petidier M Burnside ER,et al. Chondroitin sulfate proteoglycans prevent immune cell phenotypic conversion and inflammation resolution via TLR4 in rodent models of spinal cord injury[J]. Nat Commun202213(1):2933.
45
Dickendesher TL Baldwin KT Mironova YA,et al. NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans[J]. Nat Neurosci201215(5):703-712.
46
Shen YJ Tenney AP Busch SA,et al. PTPsigma is a receptor for chondroitin sulfate proteoglycan,an inhibitor of neural regeneration[J]. Science2009326(5952):592-596.
47
Ying XW Yu XL Zhu JT,et al. Water treadmill training ameliorates neurite outgrowth inhibition associated with NGR/RhoA/ROCK by inhibiting astrocyte activation following spinal cord injury[J]. Oxid Med Cell Longev20222022:1724362.
48
Wu KY Hengst U Cox LJ,et al. Local translation of RhoA regulates growth cone collapse[J]. Nature2005436(7053):1020-1024.
49
Gutekunst CA Tung JK McDougal ME,et al. C3 transferase gene therapy for continuous conditional RhoA inhibition[J]. Neuroscience2016339:308-318.
50
Ohtake Y Wong D Abdul-Muneer PM,et al. Two PTP receptors mediate CSPG inhibition by convergent and divergent signaling pathways in neurons[J]. Sci Rep20166:37152.
51
Wei YT Andrews MR. Advances in chondroitinase delivery for spinal cord repair[J]. J Integr Neurosci202221(4):118.
52
Barritt AW Davies M Marchand F,et al. Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury[J]. J Neurosci200626(42):10856-10867.
53
Hu JL Rodemer W Zhang GX,et al. Chondroitinase ABC promotes axon regeneration and reduces retrograde apoptosis signaling in lamprey[J]. Front Cell Dev Biol20219:653638.
54
Sun XM Liu HQ Tan Z,et al. Remodeling microenvironment for endogenous repair through precise modulation of chondroitin sulfate proteoglycans following spinal cord injury[J]. Small202319(6):e2205012.
55
Hettiaratchi MH O’Meara MJ Teal CJ,et al. Local delivery of stabilized chondroitinase ABC degrades chondroitin sulfate proteoglycans in stroke-injured rat brains[J]. J Control Release2019297:14-25.
56
Zhao RR Muir EM Alves JN,et al. Lentiviral vectors express chondroitinase ABC in cortical projections and promote sprouting of injured corticospinal axons[J]. J Neurosci Methods2011201(1):228-238.
57
Igarashi M Takeuchi K Sugiyama S. Roles of CSGalNAcT1,a key enzyme in regulation of CS synthesis,in neuronal regeneration and plasticity[J]. Neurochem Int2018119:77-83.
58
Li LM Zheng HP Ma XP,et al. Inhibition of astrocytic carbohydrate sulfotransferase 15 promotes nerve repair after spinal cord injury via mitigation of CSPG mediated axonal inhibition[J]. Cell Mol Neurobiol202343(6):2925-2937.
59
Zhang ZH Song ZW Luo L,et al. Photobiomodulation inhibits the expression of chondroitin sulfate proteoglycans after spinal cord injury via the Sox9 pathway[J]. Neural Regen Res202419(1):180-189.
60
Hosseini SM Alizadeh A Shahsavani N,et al. Suppressing CSPG/LAR/PTPσ axis facilitates neuronal replacement and synaptogenesis by human neural precursor grafts and improves recovery after spinal cord injury[J]. J Neurosci202242(15):3096-3121.
61
Dubreuil CI Winton MJ McKerracher L. Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system[J]. J Cell Biol2003162(2):233-243.
62
Fry EJ Chagnon MJ López-Vales R,et al. Corticospinal tract regeneration after spinal cord injury in receptor protein tyrosine phosphatase sigma deficient mice[J]. Glia201058(4):423-433.
63
Guijarro-Belmar A Viskontas M Wei YT,et al. Epac2 elevation reverses inhibition by chondroitin sulfate proteoglycans in vitro and transforms postlesion inhibitory environment to promote axonal outgrowth in an Ex vivo model of spinal cord injury[J]. J Neurosci201939(42):8330-8346.
64
Petrosyan HA Alessi V Lasek K,et al. AAV vector mediated delivery of NG2 function neutralizing antibody and neurotrophin NT-3 improves synaptic transmission,locomotion,and urinary tract function after spinal cord contusion injury in adult rats[J]. J Neurosci202343(9):1492-1508.

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