Navigating α-Synuclein Aggregation Inhibition: Methods, Mechanisms, and Molecular Targets

Chem Rec. 2023 Nov 2:e202300282. doi: 10.1002/tcr.202300282. Online ahead of print.ABSTRACTParkinson's disease is a yet incurable, age-related neurodegenerative disorder characterized by the aggregation of small neuronal protein α-synuclein into amyloid fibrils. Inhibition of this process is a prospective strategy for developing a disease-modifying treatment. We overview here small molecule, peptide, and protein inhibitors of α-synuclein fibrillization reported to date. Special attention was paid to the specificity of inhibitors and critical analysis of their action mechanisms. Namely, the importance of oxidation of polyphenols and cross-linking of α-synuclein into inhibitory dimers was highlighted. We also compared strategies of targeting monomeric, oligomeric, and fibrillar α-synuclein species, thoroughly discussed the strong and weak sides of different approaches to testing the inhibitors.PMID:37919046 | DOI:10.1002/tcr.202300282

Source: Chemical Record - November 2, 2023 Category: Chemistry Authors: Maksym Galkin Anastasiia Priss Yevhenii Kyriukha Volodymyr Shvadchak Source Type: research