帕金森病(PD)是一种进行性神经退行性疾病。PD患者的经典行为缺陷涉及运动症状,如运动迟缓,震颤,和刚性,以及非运动症状,如嗅觉缺失,抑郁症,和认知障碍。病理上,黑质(SN)中多巴胺能(DA)神经元的进行性丢失和α-突触核蛋白(α-syn)组成的路易体(LB)和路易神经突(LN)的积累是关键标志。Glia不仅仅是支持神经元的旁观者,它们积极地促进神经元发育和功能的几乎每一个方面;神经胶质失调与包括PD在内的一系列神经退行性疾病有关。重要的是,大量证据增加了胶质细胞活化和神经炎症作为PD发病和进展的新特征.因此,更好地了解胶质细胞,尤其是神经元-神经胶质串扰,不仅将提供对大脑生理事件的见解,而且还将提高我们对PD病理学的认识。这篇综述阐述了当前对PD中α-syn发病机制的理解,专注于神经元神经胶质串扰。特别是,α-syn在神经元和神经胶质之间的传递,α-syn诱导的神经胶质激活,并详细讨论了神经胶质激活对DA神经元变性的反馈。此外,α-syn聚集,铁沉积,并涵盖了调节PD中DA神经元铁性凋亡的神经胶质激活。最后,我们总结了临床前和临床治疗,尤其是针对胶质细胞,在PD治疗中。
Parkinson\'s disease (PD) is a progressive neurodegenerative disorder. The classical behavioral defects of PD patients involve motor symptoms such as bradykinesia, tremor, and rigidity, as well as non-motor symptoms such as anosmia, depression, and cognitive impairment. Pathologically, the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN) and the accumulation of α-synuclein (α-syn)-composed Lewy bodies (LBs) and Lewy neurites (LNs) are key hallmarks. Glia are more than mere bystanders that simply support neurons, they actively contribute to almost every aspect of neuronal development and function; glial dysregulation has been implicated in a series of neurodegenerative diseases including PD. Importantly, amounting evidence has added glial activation and neuroinflammation as new features of PD onset and progression. Thus, gaining a better understanding of glia, especially neuron-glia crosstalk, will not only provide insight into brain physiology events but also advance our knowledge of PD pathologies. This review addresses the current understanding of α-syn pathogenesis in PD, with a focus on neuron-glia crosstalk. Particularly, the transmission of α-syn between neurons and glia, α-syn-induced glial activation, and feedbacks of glial activation on DA neuron degeneration are thoroughly discussed. In addition, α-syn aggregation, iron deposition, and glial activation in regulating DA neuron ferroptosis in PD are covered. Lastly, we summarize the preclinical and clinical therapies, especially targeting glia, in PD treatments.