A novel autophagy modulator 6-Bio ameliorates SNCA/α-synuclein toxicity. Issue 7 (3rd July 2017)

• Record Type: Journal Article
• Authors: Suresh, S. N.; Chavalmane, Aravinda K.; DJ, Vidyadhara; Yarreiphang, Haorei; Rai, Shashank; Paul, Abhik; Clement, James P.; Alladi, Phalguni Anand; Manjithaya, Ravi
• Is Part Of: Autophagy. Volume 13:Issue 7(2017)
• Page Start: 1221
• Page End: 1234
• Publication Date: 2017-07-03
• Subjects: 6-Bio -- autolysosomes -- autophagy -- high-throughput screening -- MPTP -- neurodegeneration, SNCA -- TH; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2017.1302045
• Languages: English
• ISSNs: 1554-8627

Abstract

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.