The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive?

The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive?
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DOI:
10.1016/j.brainres.2014.09.008
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发表时间:
2015-08-18
期刊:
影响因子:
2.9
通讯作者:
Town, Terrence
Town, Terrence
中科院分区:
医学3区
文献类型:
--
作者:
Doty, Kevin R.;Guillot-Sestier, Marie-Victoire;Town, Terrence

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神经退行性疾病具有共同的特征,包括导致认知或运动功能障碍的灾难性神经元丧失。神经损伤发生在炎症环境中,炎症环境中有常驻免疫细胞,有时也有浸润性免疫细胞,所有这些细胞都参与了分泌的炎症调节剂和激活的免疫细胞表面受体之间的复杂相互作用。在最近的全基因组关联研究中,与神经变性风险增加相关的免疫因子的数量突出了这些免疫调节剂的重要性。在设计针对神经退行性疾病的免疫调节治疗策略时,比较困难的任务之一是将有益信号与有害信号区分开来。在这方面,更多地了解这些疾病的免疫成分已经产生了共同的主题。这些统一的概念最终将使基于免疫的治疗方法能够用于治疗阿尔茨海默病、帕金森病和肌萎缩侧索硬化症。有针对性的免疫调节应该可以调节适应不良因素,在神经退行性疾病的背景下实现有益的免疫反应。
Neurodegenerative diseases share common features, including catastrophic neuronal loss that leads to cognitive or motor dysfunction. Neuronal injury occurs in an inflammatory milieu that is populated by resident and sometimes, infiltrating, immune cells-all of which participate in a complex interplay between secreted inflammatory modulators and activated immune cell surface receptors. The importance of these immunomodulators is highlighted by the number of immune factors that have been associated with increased risk of neurodegeneration in recent genome-wide association studies. One of the more difficult tasks for designing therapeutic strategies for immune modulation against neurodegenerative diseases is teasing apart beneficial from harmful signals. In this regard, learning more about the immune components of these diseases has yielded common themes. These unifying concepts should eventually enable immune-based therapeutics for treatment of Alzheimer’s and Parkinson’s diseases and amyotrophic lateral sclerosis. Targeted immune modulation should be possible to temper maladaptive factors, enabling beneficial immune responses in the context of neurodegenerative diseases.
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