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

0582665 - ÚOCHB 2025 RIV eng J - Journal Article
Galkin, Maksym - Priss, Anastasiia - Kyriukha, Y. - Shvadchak, V.
Navigating α-Synuclein Aggregation Inhibition: Methods, Mechanisms, and Molecular Targets.
Chemical Record. Roč. 24, č. 2 (2024), č. článku e202300282. ISSN 1527-8999. E-ISSN 1528-0691
Institutional support: RVO:61388963
Keywords : amyloid * inhibitor * alpha-synuclein * Parkinson's disease * protein misfolding
Impact factor: 6.6, year: 2022
Method of publishing: Limited access
https://doi.org/10.1002/tcr.202300282

Parkinson's disease is a yet incurable, age-related neurodegenerative disorder characterized by the aggregation of small neuronal protein alpha-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 alpha-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 alpha-synuclein into inhibitory dimers was highlighted. We also compared strategies of targeting monomeric, oligomeric, and fibrillar alpha-synuclein species, thoroughly discussed the strong and weak sides of different approaches to testing the inhibitors.
Permanent Link: https://hdl.handle.net/11104/0350744