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

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

Autophagy (2017-03-30)
S N Suresh, Aravinda K Chavalmane, Vidyadhara Dj, Haorei Yarreiphang, Shashank Rai, Abhik Paul, James P Clement, Phalguni Anand Alladi, Ravi Manjithaya
ABSTRACT

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.

MATERIALS
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