Li Sheng, Liu Yanbing, Lu Sen, Xu Jiayi, Liu Xiaokun, Yang Di, Yang Yuxuan, Hou Lin, Li Ning
School of Basic Medicine, Qingdao University, Qingdao, China.
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, Qingdao, 266071, China.
Mol Cell Biochem. 2025 Jan;480(1):139-157. doi: 10.1007/s11010-024-04985-3. Epub 2024 Apr 16.
Parkinson's disease (PD) is an aging-associated neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies containing α-synuclein within these neurons. Oligomeric α-synuclein exerts neurotoxic effects through mitochondrial dysfunction, glial cell inflammatory response, lysosomal dysfunction and so on. α-synuclein aggregation, often accompanied by oxidative stress, is generally considered to be a key factor in PD pathology. At present, emerging evidences suggest that metabolism alteration is closely associated with α-synuclein aggregation and PD progression, and improvement of key molecules in metabolism might be potentially beneficial in PD treatment. In this review, we highlight the tripartite relationship among metabolic changes, α-synuclein aggregation, and oxidative stress in PD, and offer updated insights into the treatments of PD, aiming to deepen our understanding of PD pathogenesis and explore new therapeutic strategies for the disease.
帕金森病（PD）是一种与衰老相关的神经退行性疾病，其特征是黑质致密部多巴胺能神经元逐渐丧失，且这些神经元内存在含有α-突触核蛋白的路易小体。寡聚α-突触核蛋白通过线粒体功能障碍、胶质细胞炎症反应、溶酶体功能障碍等发挥神经毒性作用。α-突触核蛋白聚集通常伴有氧化应激，一般被认为是PD病理的关键因素。目前，新出现的证据表明，代谢改变与α-突触核蛋白聚集及PD进展密切相关，改善代谢中的关键分子可能对PD治疗具有潜在益处。在本综述中，我们重点阐述了PD中代谢变化、α-突触核蛋白聚集和氧化应激之间的三方关系，并提供了PD治疗的最新见解，旨在加深我们对PD发病机制的理解，并探索该疾病的新治疗策略。
