Yuxiang Xu1  · Tingting Han1  · Yue Wu2  · Haixuan Liu1  · Keyuan Hou1  · Zhaowu An1  · Yongjie Li3  · Chaoyang Zhu1  · Song Wang2  · Jianshe Wei1

1 Institute for Brain Sciences Research, Center for Translational Neuromedicine, School of Life Sciences, Huaihe Hospital of Henan University, Henan University, Kaifeng 475004, China 

2 Hubei Superior Discipline Group of Exercise and Brain Science from Hubei Provincial, Wuhan Sports University, Wuhan 430079, China 

3 Department of Rehabilitation Medicine, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang 550014, China

Abstract

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.

Keywords

Microglia; Neuroinflammation; Aging; Senescence-associated secretory phenotype; Parkinson’s disease; Blood–brain barrier

[SpringerLink]