Protein–protein interactions regulating α-synuclein pathology

• DOI: 10.1016/j.tins.2024.01.002
• Publication Date: 2024-02-13T21:09:57Z
• Authors: Jiannan Wang; Lijun Dai; Sichun Chen; Zhaohui Zhang; Xin Fang; Zhentao Zhang
• Keywords: Dopaminergic Neurons; alpha-Synuclein; Humans; Neurodegenerative Diseases; Parkinson Disease

Parkinson's disease (PD) is a neurodegenerative disease characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the formation of Lewy bodies (LBs). The main proteinaceous component of LBs is aggregated α-synuclein (α-syn). However, the mechanisms underlying α-syn aggregation are not yet fully understood. Converging lines of evidence indicate that, under certain pathological conditions, various proteins can interact with α-syn and regulate its aggregation. Understanding these protein-protein interactions is crucial for unraveling the molecular mechanisms contributing to PD pathogenesis. In this review we provide an overview of the current knowledge on protein-protein interactions that regulate α-syn aggregation. Additionally, we briefly summarize the methods used to investigate the influence of protein-protein interactions on α-syn aggregation and propagation.