摘要
对肌萎缩性侧索硬化(ALS)的发病机理的研究已经获得了显着的基因发现,虽然到目前为止,仅在治疗方面的进展非常有限。目前,ALS被认为是一种多因素疾病,其呈现多种临床表现,范围从单基因遗传疾病到自身免疫病理,并且伴随错误折叠的蛋白质聚集和神经炎症发展。与ALS发病相关的一个重要因素是与退行性运动神经元相关的小胶质细胞激活。这种活化导致与吞噬作用和炎症相关的大范围基因的表达的改变,以及神经元和神经胶质细胞之间的动态相互作用的深刻修饰。小胶质细胞活性的过度活化和失调导致有害作用并导致神经元死亡。然而,小胶质细胞在非炎性功能的参与挑战我们的神经炎症的概念,并开辟了新的可能性的ALS的病理生理机制的研究。在这次审查我们总结当前的知识关于神经元和小胶质细胞在ALS中的自适应相互作用。我们还讨论了控制小胶质细胞激活和神经炎症的程度可能有临床和治疗益处的条件的假说。
关键词: 肌萎缩性侧索硬化,神经炎症,小胶质细胞,星形胶质细胞,神经元相互作用
Current Medicinal Chemistry
Title:Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited
Volume: 23 Issue: 42
Author(s): Manuel J. Rodríguez, Nicole Mahy
Affiliation:
关键词: 肌萎缩性侧索硬化,神经炎症,小胶质细胞,星形胶质细胞,神经元相互作用
摘要: Research onto the pathogenesis of amyotrophic lateral sclerosis (ALS) has obtained notable gene discoveries, although, to date, only progress with regard to treatment has been very modest. Currently ALS is considered a multifactorial disease that presents diverse clinical presentations, ranging from a monogenic inherited disease to an autoimmune pathology, and develops with misfolded protein aggregation and neuroinflammation. An important factor related to ALS pathogenesis is the microglial activation associated with degenerative motor neurons. This activation leads to changes in the expression of a wide range of genes related to phagocytosis and inflammation, and to profound modifications in the dynamic interactions between neurons and glial cells. Overactivation and deregulation of microglial activity causes deleterious effects and leads to neuronal death. However, the involvement of microglia in non-inflammatory functions challenges our concept of neuroinflammation and opens up new possibilities for the study of the pathophysiological mechanisms of ALS. In this review we summarize the current knowledge on the adaptive interactions between neurons and microglia in ALS. We also discuss the hypothesis that controlling the extent of microglial activation and neuroinflammation may have clinical and therapeutic benefits for the condition.
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Cite this article as:
Manuel J. Rodríguez, Nicole Mahy , Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited, Current Medicinal Chemistry 2016; 23 (42) . https://dx.doi.org/10.2174/0929867324666161123091314
DOI https://dx.doi.org/10.2174/0929867324666161123091314 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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