The Role of Astrocytes in Multiple Sclerosis Progression.
The Role of Astrocytes in Multiple Sclerosis Progression.
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星形胶质细胞在多发性硬化症进展中的作用。
DOI：
10.3389/fneur.2015.00180
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发表时间：
2015
影响因子：
3.4
通讯作者：
Farez MF
中科院分区：
文献类型：
--
作者：
Correale J;Farez MF
多发性硬化症（MS）是一种引起中枢神经系统（CNS）脱髓鞘和轴索损伤的炎症性疾病。尽管其病因仍然难以捉摸，但有几条证据支持自身免疫在疾病发病机制中起主要作用的概念。多发性硬化症的病程变化很大；然而，大多数患者最初表现为复发缓解的临床过程。在患病10-15年后，这种模式在多达50%的未经治疗的患者中变为进行性，在此期间，临床症状缓慢地导致多年的持续恶化。然而，在大约15%的多发性硬化症患者中，疾病从发病开始就持续发展。已发表的证据支持这一概念，即进行性多发性硬化症反映了一种鲜为人知的隐性轴突变性和神经元丢失机制。最近，观察到的小胶质细胞类型和星形胶质细胞的激活和增殖表明，常驻中枢神经系统细胞可能在疾病进展中起关键作用。星形胶质细胞可能通过以下几种机制参与这一过程：(a)作为先天免疫系统的一部分，(b)作为细胞毒性因子的来源，(c)通过形成胶质瘢痕抑制髓鞘再生和轴突再生，以及(d)促进轴突线粒体功能障碍。此外，星形胶质细胞介导的调节机制可能受到衰老的影响。值得注意的是，星形胶质细胞也可能限制促炎因子的有害影响，同时为少突胶质细胞和神经元提供支持和保护。由于在星形胶质细胞效应中观察到的二分法，针对星形胶质细胞的治疗策略的设计成为一项具有挑战性的努力。因此，更好地了解星形胶质细胞的分子和功能特性，应该促进对它们在MS病理生理中的特定作用的理解，从而导致开发新的和更成功的治疗方法。
Multiple sclerosis (MS) is an inflammatory disorder causing central nervous system (CNS) demyelination and axonal injury. Although its etiology remains elusive, several lines of evidence support the concept that autoimmunity plays a major role in disease pathogenesis. The course of MS is highly variable; nevertheless, the majority of patients initially present a relapsing–remitting clinical course. After 10–15 years of disease, this pattern becomes progressive in up to 50% of untreated patients, during which time clinical symptoms slowly cause constant deterioration over a period of many years. In about 15% of MS patients, however, disease progression is relentless from disease onset. Published evidence supports the concept that progressive MS reflects a poorly understood mechanism of insidious axonal degeneration and neuronal loss. Recently, the type of microglial cell and of astrocyte activation and proliferation observed has suggested contribution of resident CNS cells may play a critical role in disease progression. Astrocytes could contribute to this process through several mechanisms: (a) as part of the innate immune system, (b) as a source of cytotoxic factors, (c) inhibiting remyelination and axonal regeneration by forming a glial scar, and (d) contributing to axonal mitochondrial dysfunction. Furthermore, regulatory mechanisms mediated by astrocytes can be affected by aging. Notably, astrocytes might also limit the detrimental effects of pro-inflammatory factors, while providing support and protection for oligodendrocytes and neurons. Because of the dichotomy observed in astrocytic effects, the design of therapeutic strategies targeting astrocytes becomes a challenging endeavor. Better knowledge of molecular and functional properties of astrocytes, therefore, should promote understanding of their specific role in MS pathophysiology, and consequently lead to development of novel and more successful therapeutic approaches.