Raj Siddharth, Sarangi Priyabrata, Goyal Divya, Kumar Hemant
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India, 382355.
ACS Pharmacol Transl Sci. 2024 Sep 19;7(10):2912-2923. doi: 10.1021/acsptsci.4c00192. eCollection 2024 Oct 11.
Disruption of myelin, the fatty sheath-insulating nerve fibers in the white matter, blocks or slows the rapid transmission of electrical signals along nerve cells and contributes to several neurodegenerative diseases such as multiple sclerosis. Traditionally, research has focused on neuronal dysfunction as the primary factor, including autoimmunity, infections, inflammation, and genetic disorders causing demyelination. However, recent insights emphasize the critical role of pericytes, non-neuronal cells that regulate blood flow and maintain the health of blood vessels within white matter. This Perspective explores the principal mechanisms through which pericyte dysfunction contributes to damage and demyelination, including impaired communication with neurons (neurovascular uncoupling), excessive formation of scar tissue (fibrosis), and the infiltration of detrimental substances from the bloodstream. Understanding these mechanisms of pericyte-driven demyelination may lead to the creation of new therapeutic strategies for tackling a range of neurodegenerative conditions.
髓磷脂是白质中包裹神经纤维的脂肪鞘，其破坏会阻碍或减缓电信号沿神经细胞的快速传递，并导致多种神经退行性疾病，如多发性硬化症。传统上，研究主要集中在神经元功能障碍这一主要因素上，包括自身免疫、感染、炎症以及导致脱髓鞘的遗传疾病。然而，最近的研究发现强调了周细胞的关键作用，周细胞是一种非神经元细胞，可调节血流并维持白质内血管的健康。本观点探讨了周细胞功能障碍导致损伤和脱髓鞘的主要机制，包括与神经元的通讯受损（神经血管解偶联）、瘢痕组织过度形成（纤维化）以及有害物质从血液中的渗入。了解这些由周细胞驱动的脱髓鞘机制可能会带来针对一系列神经退行性疾病的新治疗策略。
