Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Front Immunol. 2022 Apr 26;13:856376. doi: 10.3389/fimmu.2022.856376. eCollection 2022.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease worldwide, characterized by progressive neuron degeneration or loss due to excessive accumulation of β-amyloid (Aβ) peptides, formation of neurofibrillary tangles (NFTs), and hyperphosphorylated tau. The treatment of AD has been only partially successful as the majority of the pharmacotherapies on the market may alleviate some of the symptoms. In the occurrence of AD, increasing attention has been paid to neurodegeneration, while the resident glial cells, like microglia are also observed. Microglia, a kind of crucial glial cells associated with the innate immune response, functions as double-edge sword role in CNS. They exert a beneficial or detrimental influence on the adjacent neurons through secretion of both pro-inflammatory cytokines as well as neurotrophic factors. In addition, their endocytosis of debris and toxic protein like Aβ and tau ensures homeostasis of the neuronal microenvironment. In this review, we will systematically summarize recent research regarding the roles of microglia in AD pathology and latest microglia-associated therapeutic targets mainly including pro-inflammatory genes, anti-inflammatory genes and phagocytosis at length, some of which are contradictory and controversial and warrant to further be investigated.
阿尔茨海默病（AD）是全球最常见的神经退行性疾病，其特征是由于β-淀粉样蛋白（Aβ）肽的过度积累、神经原纤维缠结（NFT）的形成以及过度磷酸化的 tau 的形成，导致神经元进行性退化或丧失。AD 的治疗仅部分成功，因为市场上的大多数药物疗法可能只能缓解一些症状。在 AD 的发生过程中，人们越来越关注神经退行性变，而同时也观察到了神经胶质细胞中的小胶质细胞。小胶质细胞是一种与先天免疫反应相关的重要胶质细胞，在中枢神经系统中具有双刃剑的作用。它们通过分泌促炎细胞因子和神经营养因子，对相邻神经元产生有益或有害的影响。此外，它们对 Aβ和 tau 等碎片和毒性蛋白的内吞作用确保了神经元微环境的平衡。在这篇综述中，我们将系统地总结小胶质细胞在 AD 病理中的作用以及最新的小胶质细胞相关治疗靶点的研究进展，主要包括促炎基因、抗炎基因和吞噬作用，其中一些是相互矛盾和有争议的，需要进一步研究。
