Li Wu, Yong-Yan Xie, Jia-Xin Mu, Shu-Chao Ge, Li-Ping Huang
School of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, NanChang, China.
School of Pharmacy, Jiangxi University of Chinese Medicine, NanChang, China.
Brain Res. 2025 Mar 15;1851:149480. doi: 10.1016/j.brainres.2025.149480. Epub 2025 Jan 28.
Ageing is a major risk factor for neurodegenerative diseases like Alzheimer's disease (AD). Microglia, as the principal innate immune cells within the brain, exert homeostatic and active immunological defense functions throughout human lifespan. The age-related dysfunction of microglia is currently recognized as a pivotal trigger for brain diseases associated with aging. In AD, microglia exhibit alterations in gene expression, cellular morphology, and functional behavior. By focusing on the immunomodulatory functions of factors secreted by senescent microglia, such as cytokines, chemokines, complement factors, and reactive oxygen species (ROS), we explore the diverse detrimental effects of microglia in aging and AD pathogenesis, including Aβ accumulation, Tau deposition, synaptic dysfunction, and neuroinflammation. These collectively contribute to hastening the progression of. In this review, we highlight the key role of senescent microglia in the pathological processes of AD. Then we propose that targeting senescent microglia holds great promise for therapeutic interventions in neurodegenerative diseases.
衰老是阿尔茨海默病（AD）等神经退行性疾病的主要风险因素。小胶质细胞作为大脑内主要的固有免疫细胞，在人类整个生命周期中发挥着稳态和主动免疫防御功能。小胶质细胞与年龄相关的功能障碍目前被认为是与衰老相关的脑部疾病的关键触发因素。在AD中，小胶质细胞在基因表达、细胞形态和功能行为方面表现出改变。通过关注衰老小胶质细胞分泌的因子（如细胞因子、趋化因子、补体因子和活性氧（ROS））的免疫调节功能，我们探讨了小胶质细胞在衰老和AD发病机制中的各种有害作用，包括Aβ积累、Tau沉积、突触功能障碍和神经炎症。这些共同导致疾病进展加速。在这篇综述中，我们强调了衰老小胶质细胞在AD病理过程中的关键作用。然后我们提出，针对衰老小胶质细胞有望为神经退行性疾病的治疗干预带来巨大希望。
