PDF(Pubmed)
Abstract：
Parkinson\'s disease (PD) is a common neurodegenerative pathology whose major clinical symptoms are movement disorders. The main pathological characteristics of PD are the selective death of dopaminergic (DA) neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies containing α-synuclein (α-Syn) within these neurons. PD is associated with numerous risk factors, including environmental factors, genetic mutations and aging. In many cases, the complex interplay of numerous risk factors leads to the onset of PD. The mutated α-Syn gene, which expresses pathologicalα-Syn protein, can cause PD. Another important feature of PD is neuroinflammation, which is conducive to neuronal death. α-Syn is able to interact with certain cell types in the brain, including through phagocytosis and degradation of α-Syn by glial cells, activation of inflammatory pathways by α-Syn in glial cells, transmission of α-Syn between glial cells and neurons, and interactions between peripheral immune cells and α-Syn. In addition to the aforementioned risk factors, PD may also be associated with aging, as the prevalence of PD increases with advancing age. The aging process impairs the cellular clearance mechanism, which leads to chronic inflammation and the accumulation of intracellular α-Syn, which results in DA neuronal death. In the present review, the age-associated α-Syn pathogenicity and the interactions between α-Syn and certain types of cells within the brain are discussed to facilitate understanding of the mechanisms of PD pathogenesis, which may potentially provide insight for the future clinical treatment of PD.
摘要：
帕金森病(Parkinson’sdisease,PD)是一种常见的神经退行性疾病,其主要临床症状为运动障碍。PD的主要病理特征是黑质致密部中多巴胺能（DA）神经元的选择性死亡，以及这些神经元中存在含有α-突触核蛋白（α-Syn）的路易体。PD与许多危险因素有关，包括环境因素，基因突变和衰老。在许多情况下,众多危险因素的复杂相互作用导致PD的发作.突变的α-Syn基因,表达病理α-Syn蛋白，会导致PD。PD的另一个重要特征是神经炎症，这有助于神经元死亡。α-Syn能够与大脑中的某些细胞类型相互作用，包括通过神经胶质细胞吞噬和降解α-Syn，神经胶质细胞中α-Syn激活炎症途径，α-Syn在神经胶质细胞和神经元之间的传递，以及外周免疫细胞与α-Syn之间的相互作用。除上述风险因素外，PD也可能与衰老有关，PD的患病率随着年龄的增长而增加。衰老过程损害了细胞清除机制，导致慢性炎症和细胞内α-Syn的积累，导致DA神经元死亡。在本次审查中，讨论了与年龄相关的α-Syn致病性以及α-Syn与大脑中某些类型细胞之间的相互作用，以促进对PD发病机制的理解。这可能为未来PD的临床治疗提供潜在的见解。
