Department of Neurology, Kindai University Faculty of Medicine, Osaka-Sayama 589-8511, Osaka, Japan.
Department of Neurology, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan.
Int J Mol Sci. 2024 Aug 16;25(16):8935. doi: 10.3390/ijms25168935.
Aggregation of α-synuclein (αSyn) and its accumulation as Lewy bodies play a central role in the pathogenesis of Parkinson's disease (PD). However, the mechanism by which αSyn aggregates in the brain remains unclear. Biochemical studies have demonstrated that αSyn interacts with lipids, and these interactions affect the aggregation process of αSyn. Furthermore, genetic studies have identified mutations in lipid metabolism-associated genes such as glucocerebrosidase 1 (GBA1) and synaptojanin 1 (SYNJ1) in sporadic and familial forms of PD, respectively. In this review, we focus on the role of lipids in triggering αSyn aggregation in the pathogenesis of PD and propose the possibility of modulating the interaction of lipids with αSyn as a potential therapy for PD.
α-突触核蛋白（αSyn）的聚集及其作为路易体的积累在帕金森病（PD）的发病机制中起着核心作用。然而，αSyn 在大脑中聚集的机制仍不清楚。生化研究表明，αSyn 与脂质相互作用，这些相互作用影响 αSyn 的聚集过程。此外，遗传研究分别在散发性和家族性 PD 中鉴定到与脂质代谢相关基因（如葡萄糖脑苷脂酶 1（GBA1）和突触结合蛋白 1（SYNJ1））的突变。在这篇综述中，我们重点讨论了脂质在触发 PD 发病机制中 αSyn 聚集的作用，并提出了调节脂质与 αSyn 相互作用的可能性，作为 PD 的一种潜在治疗方法。
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