Unknown

Dataset Information

0

ZPD-2, a Small Compound That Inhibits ?-Synuclein Amyloid Aggregation and Its Seeded Polymerization.


ABSTRACT: ?-Synuclein (?-Syn) forms toxic intracellular protein inclusions and transmissible amyloid structures in Parkinson's disease (PD). Preventing ?-Syn self-assembly has become one of the most promising approaches in the search for disease-modifying treatments for this neurodegenerative disorder. Here, we describe the capacity of a small molecule (ZPD-2), identified after a high-throughput screening, to inhibit ?-Syn aggregation. ZPD-2 inhibits the aggregation of wild-type ?-Syn and the A30P and H50Q familial variants in vitro at substoichiometric compound:protein ratios. In addition, the molecule prevents the spreading of ?-Syn seeds in protein misfolding cyclic amplification assays. ZPD-2 is active against different ?-Syn strains and blocks their seeded polymerization. Treating with ZPD-2 two different PD Caenorhabditis elegans models that express ?-Syn either in muscle or in dopaminergic (DA) neurons substantially reduces the number of ?-Syn inclusions and decreases synuclein-induced DA neurons degeneration. Overall, ZPD-2 is a hit compound worth to be explored in order to develop lead molecules for therapeutic intervention in PD.

SUBMITTER: Pena-Diaz S 

PROVIDER: S-EPMC6928008 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

Similar Datasets

2020-01-01 | S-EPMC7597392 | BioStudies
2018-01-01 | S-EPMC6187188 | BioStudies
2014-01-01 | S-EPMC4230739 | BioStudies
2018-01-01 | S-EPMC5820349 | BioStudies
1000-01-01 | S-EPMC4110482 | BioStudies
2016-01-01 | S-EPMC4920419 | BioStudies
1000-01-01 | S-EPMC5855556 | BioStudies
2021-08-13 | E-MTAB-7302 | ArrayExpress
1000-01-01 | S-EPMC4119404 | BioStudies
2019-01-01 | S-EPMC6892271 | BioStudies