xct790 and 6-bromoindirubin-3--oxime

Aggrephagy is a selective autophagic degradation intracellular mechanism that clears toxic misfolded protein aggregates such as α-synuclein. Here, we identify and demonstrate that the small molecule, XCT 790 alleviates α-synuclein-mediated adverse effects in a yeast model of proteotoxicity. XCT 790 induced general autophagy and also enhanced starvation-induced autophagy. Mechanistically, we showed that XCT 790 clears toxic α-synuclein aggregates in an autophagy-dependent manner. Interestingly, XCT 790 did not demonstrate a synergistic effect on autophagy induction in the presence of another autophagy inducer such as 6-Bio.

Topics: alpha-Synuclein; Cytoprotection; Indoles; Macroautophagy; Models, Biological; Nitriles; Oximes; Protein Aggregates; Proteolysis; Saccharomyces cerevisiae; Thiazoles