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
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
Rights Holder
Jemil Ahmed, Tessa C. Fitch, Courtney M. Donnelly, Johnson A. Joseph, Tyler D. Ball, Mikaela M. Bassil, Ahyun Son, Chen Zhang, Aurélie Ledreux, Scott Horowitz, Yan Qin, Daniel Paredes, Sunil Kumar
Provenance
Received from author
File Format
application/pdf
Language
English (eng)
Extent
16 pgs
File Size
6.0 MB
Publication Title
Nature Communications
First Page
1
Last Page
17
ISSN
2041-1723
Recommended Citation
Ahmed, Jemil; Fitch, Tessa C.; Donnelly, Courtney M.; Joseph, Johnson A.; Ball, Tyler D.; Bassil, Mikaela M.; Son, Ahyun; Zhang, Chen; Ledreux, Aurélie; Horowitz, Scott; Qin, Yan; Paredes, Daniel; and Kumar, Sunil, "Foldamers Reveal and Validate Therapeutic Targets Associated with Toxic α-Synuclein Self-Assembly" (2022). Chemistry and Biochemistry: Faculty Scholarship. 129.
https://digitalcommons.du.edu/chemistryandbiochemistryfaculty/129
https://doi.org/10.1038/s41467-022-29724-4
DOI Link
https://doi.org/10.1038/s41467-022-29724-4