Parkinson's disease is caused by misfolding of the neuronal protein α-synuclein into amyloid fibrils. Unfortunately, the disease is yet incurable, and all treatments are only symptomatic. One of the possible strategies to stop Parkinson's disease progression is blocking α-synuclein misfolding.
Volodymyr Shvadchak from IOCB Prague and his colleagues used the recent CryoEM structural data to design a small protein that selectively binds to misfolded αSyn at the amyloid fibril ends preventing fibril growth. The novel inhibitor shows high specificity and is active at low nanomolar concentrations, which makes it more efficient than any other inhibitors of α-synuclein fibrillization reported to date.
The research and the results are published in the Journal of Medicinal Chemistry with Anastasiia Priss as the first author.
Read the paper:
- Priss, A.; Afitska, K.; Galkin, M.; Yushchenko, D. A.; Shvadchak, V. V. Rationally Designed Protein-Based Inhibitor of α-Synuclein Fibrillization in Cells. Journal of Medicinal Chemistry 2021, 64, 6827-6837. https://doi.org/10.1021/acs.jmedchem.1c00086
