小胶质细胞在帕金森病中的双向作用:神经保护和疾病恶化

Microglial involvement in Parkinson’s disease progression:Neuroprotection and disease aggravation

帕金森病(PD)是一种常见的与年龄相关的神经退行性疾病,其特点是黑质致密部内多巴胺能神经元的进行性丢失以及路易小体的积累。多巴胺能神经元的退化导致纹状体的多巴胺水平降低,最终出现静息性震颤、运动迟缓、肌肉僵硬和姿势不稳等运动症状,以及认知能力下降、嗅觉功能受损、精神异常和睡眠障碍等非运动症状。由于人口结构转变和全球老龄化,PD的不断增加对患者、家庭和社会构成重大负担。尽管广泛的研究已阐明了PD的病因学和潜在机制,但现有治疗主要集中在症状管理,无法阻止疾病的进展。小胶质细胞作为脑内重要的免疫细胞,对维持中枢神经系统的稳态具有关键作用。本文综述了PD研究,包括其病因学因素、分子机制和现有治疗策略。此外,审视了在PD样模型中涉及小胶质细胞的研究,深入探讨了小胶质细胞在疾病进展中的动态,并探究了小胶质细胞在促进或减轻疾病进展方面所扮演的错综角色。通过这样的探讨,本综述旨在为PD复杂的发病机制提供新的洞见和观点,激发出针对性治疗干预的创新思路。

Parkinson’s disease(PD),a prevalent age-related neurodegenerative disorder,is characterized by the progressive loss of dopaminergic neurons within the substantia nigra compacta(SNc)and the accumulation of Lewy bodies.The degeneration of dopaminergic neurons leads to diminished striatal dopamine levels,culminating in motor symptoms such as resting tremors,bradykinesia,muscle rigidity and postural instability,alongside non-motor manifestations encompassing cognitive decline,impaired olfactory function,psychological abnormalities and sleep disturbances.The escalating incidence of PD due to shifting demographics and global aging poses substantial burdens on patients,families and society.Although extensive research has elucidated the etiology and underlying mechanisms of PD,available treatments largely focus on symptom management and lack the capacity to halt disease progression.Microglia,as integral immune cells within the brain,wield pivotal influence over central nervous system homeostasis.This review presents a comprehensive synthesis of PD,encompassing its etiological factors,molecular mechanisms,and existing therapeutic strategies.Furthermore,we scrutinized research involving microglia in PD-like models,delving into the dynamics of microglia in disease progression and probing into the intricate roles that microglia assume in either fostering or mitigating disease advancement.By doing so,this review aims to furnish novel insights and perspectives that shed light on the intricate pathogenesis of PD,potentially sparking innovative concepts for targeted therapeutic interventions.