Xu Yuxiang, Han Tingting, Wu Yue, Liu Haixuan, Hou Keyuan, An Zhaowu, Li Yongjie, Zhu Chaoyang, Wang Song, Wei Jianshe
Institute for Brain Sciences Research, Center for Translational Neuromedicine, School of Life Sciences, Huaihe Hospital of Henan University, Henan University, Kaifeng, 475004, China.
Hubei Superior Discipline Group of Exercise and Brain Science from Hubei Provincial, Wuhan Sports University, Wuhan, 430079, China.
Neurosci Bull. 2025 Sep 19. doi: 10.1007/s12264-025-01505-1.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons, and its prevalence is increasing, alongside global population aging. Neuroinflammation has been widely recognized as a pivotal contributor to PD pathogenesis, particularly owing to the dual role of microglia in this process. This review systematically identifies the multiple factors regulating microglial function and phenotype, thereby driving PD initiation and progression. Furthermore, aging, a major risk factor for PD, and its profound effects on microglial state and functional dynamics are discussed. Notably, microglial hyperactivation is shown to establish a self-perpetuating cycle of "inflammation-damage-reinflammation" through the excessive release of pro-inflammatory cytokines and chemokines, which exacerbates neuronal degeneration. Lastly, the potential therapeutic strategies targeting microglial dysfunction, including interventions against the senescence-associated secretory phenotype and the modulation of microglial activity, are summarized. By elucidating how multifactorial alterations in microglial states influence PD pathology, this review provides novel insights and directions for advancing therapeutic research in PD.
帕金森病（PD）是一种以多巴胺能神经元丧失为特征的神经退行性疾病，随着全球人口老龄化，其患病率正在上升。神经炎症已被广泛认为是PD发病机制的关键因素，尤其是由于小胶质细胞在此过程中发挥的双重作用。本综述系统地确定了调节小胶质细胞功能和表型的多种因素，从而推动了PD的发生和发展。此外，还讨论了衰老这一PD的主要危险因素及其对小胶质细胞状态和功能动态的深远影响。值得注意的是，小胶质细胞过度激活通过促炎细胞因子和趋化因子的过度释放，建立了一个“炎症-损伤-再炎症”的自我延续循环，加剧了神经元变性。最后，总结了针对小胶质细胞功能障碍的潜在治疗策略，包括针对衰老相关分泌表型的干预措施和对小胶质细胞活性的调节。通过阐明小胶质细胞状态的多因素改变如何影响PD病理，本综述为推进PD治疗研究提供了新的见解和方向。
