Proteoglycans and Glycosaminoglycans in Central Nervous System Injury.
Proteoglycans and Glycosaminoglycans in Central Nervous System Injury.
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DOI：
10.1152/ajpcell.00053.2022
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发表时间：
2022-05
期刊：
影响因子：
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通讯作者：
N. Siddiqui;K. Oshima;J. Hippensteel
中科院分区：
文献类型：
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作者：
N. Siddiqui;K. Oshima;J. Hippensteel
大脑和脊髓构成了中枢神经系统（CNS），当受伤时，可能是极具破坏性的。蛋白聚糖（PG）及其糖胺聚糖（GAG）侧链在此类损伤中的机制作用已被广泛研究。CNS损伤立即改变内皮和细胞外基质（ECM）PG和GAG。随后，这些改变导致急性损伤、损伤后纤维化和损伤后修复。这些作用是中枢神经系统损伤的病理生理学的核心。本文综述了PGs和GAGs在多种形式的损伤中的重要性，包括创伤性脑损伤、脊髓损伤和中风。我们强调的原因和后果的PG和GAG丰富的内皮糖萼在早期损伤的降解，并讨论了多效性的作用，PG在神经炎症。随后，我们评估了PG对恢复的双重作用：PG/GAG介导的抑制和促进修复。然后，我们报告了有前途的治疗策略，可能证明有效的修复中枢神经系统损伤，包括PG受体抑制，内源性，促修复PG和GAG的交付，并直接降解病理性GAG。最后，我们讨论了两个PG和GAG的ECM结构（突触和神经元周围网）在中枢神经系统损伤和恢复的重要性。
The brain and spinal cord constitute the central nervous system (CNS), which when injured, can be exceedingly devastating. The mechanistic roles of proteoglycans (PGs) and their glycosaminoglycan (GAG) side chains in such injuries have been extensively studied. CNS injury immediately alters endothelial and extracellular matrix (ECM) PGs and GAGs. Subsequently, these alterations contribute to acute injury, post-injury fibrosis, and post-injury repair. These effects are central to the pathophysiology of CNS injury. This review focuses on the importance of PGs and GAGs in multiple forms of injury including traumatic brain injury, spinal cord injury, and stroke. We highlight the causes and consequences of degradation of the PG and GAG-enriched endothelial glycocalyx in early injury and discuss the pleiotropic roles of PGs in neuroinflammation. We subsequently evaluate the dualistic effects of PGs on recovery: both PG/GAG-mediated inhibition and facilitation of repair. We then report promising therapeutic strategies that may prove effective for repair of CNS injury including PG receptor inhibition, delivery of endogenous, pro-repair PGs and GAGs, and direct degradation of pathologic GAGs. Last, we discuss importance of two PG- and GAG-containing ECM structures (synapses and perineuronal nets) in CNS injury and recovery.