Foldamers Reveal and Validate Novel Therapeutic Targets Associated with Toxic α-Synuclein Self-Assembly

Autor: Bassil Mm, Ledreux A, Jemil Ahmed, Fitch Tc, Joseph Ja, Paredes D, Yan Qin, Donnelly Cm, Sunil Kumar, Scott Horowitz, Ahyun Son, C Zhang
Rok vydání: 2021
Předmět:
DOI: 10.1101/2021.05.08.443146
Popis: 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 novel targets that are essential for aggregation and will have significant therapeutic implications. An extensive array of in vitro, ex vivo, and in vivo assays was 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 novel and effective treatments for PD.
Databáze: OpenAIRE