전한울
2024년 3월 1일
- Aggregates of α-synuclein (α-syn) are among the hallmarks of Parkinson’s disease (PD) and the main component of Lewy bodies (LBs). However, the mechanisms underlying α-syn aggregation are not fully understood.
Various proteins interact with α-Syn and alter its structural properties.
Protein–protein interactions affect the aggregation rate of α-syn and/or the toxicity of α-syn aggregates. These differences in aggregation rate and toxicity might be one of the molecular mechanisms underlying the clinical heterogeneity of PD.
Elucidating the role of protein–protein interactions in α-syn aggregation may provide insights into novel therapeutic targets for PD.
https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(24)00014-6
Abstract
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.