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XCT 790 is a pharmacological aggrephagy inducer in a yeast model of proteotoxicity
S N Suresh1,2, Monala Jayaprakash Rao1, Ravi Manjithaya1,3
1Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, India.
Abstract:
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.

