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α7烟碱受体激动剂调节神经退行性疾病中神经炎症的治疗潜力。

Therapeutic potential of α7 nicotinic receptor agonists to regulate neuroinflammation in neurodegenerative diseases.

作者信息

Foucault-Fruchard Laura, Antier Daniel

机构信息

UMR INSERM U930, Université François Rabelais, Tours, France.

CHRU de Tours, Hôpital Bretonneau, Tours, France.

出版信息

Neural Regen Res. 2017 Sep;12(9):1418-1421. doi: 10.4103/1673-5374.215244.

Abstract

Neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's diseases, are all characterized by a component of innate immunity called neuroinflammation. Neuronal loss and neuroinflammation are two phenomena closely linked. Hence, the neuroinflammation is a relevant target for the management of the neurodegenerative diseases given that, to date, there is no treatment to stop neuronal loss. Several studies have investigated the potential effects of activators of alpha 7 nicotinic acetylcholine receptors in animal models of neurodegenerative diseases. These receptors are widely distributed in the central nervous system. After activation, they seem to mediate the cholinergic anti-inflammatory pathway in the brain. This anti-inflammatory pathway, first described in periphery, regulates activation of microglial cells considered as the resident macrophage population of the central nervous system. In this article, we shortly review the agonists of the alpha 7 nicotinic acetylcholine receptors that have been evaluated and we focused on the selective positive allosteric modulators of these receptors. These compounds represent a key element to enhance receptor activity only in the presence of the endogenous agonist.

摘要

神经退行性疾病,如阿尔茨海默病、帕金森病和亨廷顿病,都具有一种称为神经炎症的固有免疫成分。神经元丧失和神经炎症是密切相关的两种现象。因此,鉴于目前尚无阻止神经元丧失的治疗方法,神经炎症是神经退行性疾病治疗的一个相关靶点。多项研究调查了α7烟碱型乙酰胆碱受体激活剂在神经退行性疾病动物模型中的潜在作用。这些受体广泛分布于中枢神经系统。激活后,它们似乎介导大脑中的胆碱能抗炎途径。这种抗炎途径最初在外周被描述,可调节被视为中枢神经系统常驻巨噬细胞群体的小胶质细胞的激活。在本文中,我们简要回顾已被评估的α7烟碱型乙酰胆碱受体激动剂,并重点关注这些受体的选择性正变构调节剂。这些化合物是仅在内源性激动剂存在时增强受体活性的关键要素。

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