Publication Date

4-27-2022

Document Type

Article

Organizational Units

College of Natural Science and Mathematics, Biological Sciences, Chemistry and Biochemistry, Knoebel Institute for Healthy Aging

Keywords

Parkinson’s disease, Alpha-Synuclein aggregation

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder for which there is no successful prevention or intervention. The pathological hallmark for PD involves the self-assembly of functional Alpha-Synuclein (αS) into non-functional amyloid structures. One of the potential therapeutic interventions against PD is the effective inhibition of αS aggregation. However, the bottleneck towards achieving this goal is the identification of αS domains/sequences that are essential for aggregation. Using a protein mimetic approach, we have identified αS sequences-based targets that are essential for aggregation and will have significant therapeutic implications. An extensive array of in vitro, ex vivo, and in vivo assays is utilized to validate αS sequences and their structural characteristics that are essential for aggregation and propagation of PD phenotypes. The study aids in developing significant mechanistic and therapeutic insights into various facets of αS aggregation, which will pave the way for effective treatments for PD.

Copyright Statement / License for Reuse

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Publication Statement

This article was originally published as:

Ahmed, J., Fitch, T. C., Donnelly, C. M., Joseph, J. A., Ball, T. D., Bassil, M. M., Son, A., Zhang, C., Ledreux, A., Horowitz, S., Qin, Y., Paredes, D., & Kumar, S. (2022). Foldamers reveal and validate therapeutic targets associated with toxic α-synuclein self-assembly. Nature Communications, 13, 2273. https://doi.org/10.1038/s41467-022-29724-4

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