Department of Biological Sciences (Pharmacology and Toxicology), National Institute of Pharmaceutical Education and Research, Hyderabad, 500037, Telangana, India.
Faillace Department of Psychiatry and Behavioural Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
Inflammopharmacology. 2024 Oct;32(5):2781-2800. doi: 10.1007/s10787-024-01550-8. Epub 2024 Aug 21.
The neurobiology of Alzheimer's disease (AD) is unclear due to its multifactorial nature. Although a wide range of studies revealed several pathomechanisms of AD, dementia is yet unmanageable with current pharmacotherapies. The recent growing literature illustrates the role of microglia-mediated neuroinflammation in the pathogenesis of AD. Indeed, microglia serve as predominant sentinels of the brain, which diligently monitor the neuroimmune axis by phagocytosis and releasing soluble factors. In the case of AD, microglial cells are involved in synaptic pruning and remodeling by producing inflammatory mediators. The conditional inter-transformation of classical activation (proinflammatory) or alternative activation (anti-inflammatory) microglia is responsible for most brain disorders. In this review, we discussed the role of microglia in neuroinflammatory processes in AD following the accumulation of amyloid-β and tau proteins. We also described the prominent phenotypes of microglia, such as disease-associated microglia (DAM), dark microglia, interferon-responsive microglia (IRMs), human AD microglia (HAMs), and microglial neurodegenerative phenotype (MGnD), which are closely associated with AD incidence. Considering the key role of microglia in AD progression, microglial-based therapeutics may hold promise in mitigating cognitive deficits by addressing the neuroinflammatory responses.
阿尔茨海默病（AD）的神经生物学机制尚不清楚，因为它具有多因素的性质。尽管广泛的研究揭示了 AD 的几种病理机制，但目前的药物治疗仍无法治疗痴呆症。最近越来越多的文献表明，小胶质细胞介导的神经炎症在 AD 的发病机制中起作用。事实上，小胶质细胞作为大脑的主要哨兵，通过吞噬和释放可溶性因子来积极监测神经免疫轴。在 AD 的情况下，小胶质细胞通过产生炎症介质参与突触修剪和重塑。经典激活（促炎）或替代激活（抗炎）小胶质细胞的条件相互转化是大多数脑疾病的原因。在这篇综述中，我们讨论了小胶质细胞在淀粉样蛋白-β和 tau 蛋白积累后 AD 中的神经炎症过程中的作用。我们还描述了小胶质细胞的主要表型，如疾病相关小胶质细胞（DAM）、暗小胶质细胞、干扰素反应性小胶质细胞（IRMs）、人类 AD 小胶质细胞（HAMs）和小胶质细胞神经退行性表型（MGnD），它们与 AD 的发生密切相关。考虑到小胶质细胞在 AD 进展中的关键作用，基于小胶质细胞的治疗方法可能通过解决神经炎症反应，有希望减轻认知障碍。
