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A novel autophagy modulator 6-Bio ameliorates SNCA/α-synuclein toxicity

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journal contribution
posted on 2017-03-28, 15:12 authored by S. N. Suresh, Aravinda K. Chavalmane, Vidyadhara DJ, Haorei Yarreiphang, Shashank Rai, Abhik Paul, James P. Clement, Phalguni Anand Alladi, Ravi Manjithaya

Parkinson disease (PD) is a life-threatening neurodegenerative movement disorder with unmet therapeutic intervention. We have identified a small molecule autophagy modulator, 6-Bio that shows clearance of toxic SNCA/α-synuclein (a protein implicated in synucleopathies) aggregates in yeast and mammalian cell lines. 6-Bio induces autophagy and dramatically enhances autolysosome formation resulting in SNCA degradation. Importantly, neuroprotective function of 6-Bio as envisaged by immunohistology and behavior analyses in a preclinical model of PD where it induces autophagy in dopaminergic (DAergic) neurons of mice midbrain to clear toxic protein aggregates suggesting that it could be a potential therapeutic candidate for protein conformational disorders.

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