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胶质细胞在肌萎缩侧索硬化症中的多方面作用。

The multifaceted role of glial cells in amyotrophic lateral sclerosis.

机构信息

Department of Neuropathology, German Center for Neurodegenerative Diseases (DZNE), Paul-Ehrlich-Strasse 17, 72076, Tübingen, Germany.

出版信息

Cell Mol Life Sci. 2014 Jan;71(2):287-97. doi: 10.1007/s00018-013-1429-7. Epub 2013 Aug 3.

Abstract

Despite indisputable progress in the molecular and genetic aspects of amyotrophic lateral sclerosis (ALS), a mechanistic comprehension of the neurodegenerative processes typical of this disorder is still missing and no effective cures to halt the progression of this pathology have yet been developed. Therefore, it seems that a substantial improvement of the outcome of ALS treatments may depend on a better understanding of the molecular mechanisms underlying neuronal pathology and survival as well as on the establishment of novel etiological therapeutic strategies. Noteworthy, a convergence of recent data from multiple studies suggests that, in cellular and animal models of ALS, a complex pathological interplay subsists between motor neurons and their non-neuronal neighbours, particularly glial cells. These observations not only have drawn attention to the physiopathological changes glial cells undergo during ALS progression, but they have moved the focus of the investigations from intrinsic defects and weakening of motor neurons to glia-neuron interactions. In this review, we summarize the growing body of evidence supporting the concept that different glial populations are critically involved in the dreadful chain of events leading to motor neuron sufferance and death in various forms of ALS. The outlined observations strongly suggest that glial cells can be the targets for novel therapeutic interventions in ALS.

摘要

尽管在肌萎缩侧索硬化症(ALS)的分子和遗传方面取得了无可争议的进展,但对这种疾病特有的神经退行性过程的机制理解仍未达成,也尚未开发出有效的治疗方法来阻止这种病理的进展。因此,似乎 ALS 治疗效果的实质性改善可能取决于对神经元病理学和存活的分子机制的更好理解,以及对新的病因治疗策略的建立。值得注意的是,来自多个研究的最新数据的汇聚表明,在 ALS 的细胞和动物模型中,运动神经元及其非神经元邻居(特别是神经胶质细胞)之间存在着复杂的病理性相互作用。这些观察结果不仅引起了人们对神经胶质细胞在 ALS 进展过程中发生的生理病理变化的关注,而且将研究的重点从运动神经元的内在缺陷和弱化转移到了胶质细胞-神经元的相互作用上。在这篇综述中,我们总结了越来越多的证据支持这样一个概念,即不同的神经胶质细胞群体在导致运动神经元遭受痛苦和死亡的各种形式的 ALS 中所经历的一连串可怕事件中起着至关重要的作用。所概述的观察结果强烈表明,神经胶质细胞可能是 ALS 中新型治疗干预的靶点。

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