title: A novel autophagy modulator 6-Bio ameliorates SNCA/α-synuclein toxicity.
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.
authors.affiliation: a Molecular Biology and Genetics Unit , Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bangalore , India.
authors.forename: S N
authors.initials: SN
authors.lastname: Suresh
authors.affiliation: a Molecular Biology and Genetics Unit , Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bangalore , India.
authors.forename: Aravinda K
authors.initials: AK
authors.lastname: Chavalmane
authors.affiliation: c Department of Neurophysiology , National Institute of Mental Health and Neuro Sciences , Bangalore , India.
authors.forename: Vidyadhara
authors.initials: V
authors.lastname: Dj
authors.affiliation: c Department of Neurophysiology , National Institute of Mental Health and Neuro Sciences , Bangalore , India.
authors.forename: Haorei
authors.initials: H
authors.lastname: Yarreiphang
authors.affiliation: a Molecular Biology and Genetics Unit , Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bangalore , India.
authors.forename: Shashank
authors.initials: S
authors.lastname: Rai
authors.affiliation: b Neuroscience Unit , Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bangalore , India.
authors.forename: Abhik
authors.initials: A
authors.lastname: Paul
authors.affiliation: b Neuroscience Unit , Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bangalore , India.
authors.forename: James P
authors.initials: JP
authors.lastname: Clement
authors.affiliation: c Department of Neurophysiology , National Institute of Mental Health and Neuro Sciences , Bangalore , India.
authors.forename: Phalguni Anand
authors.initials: PA
authors.lastname: Alladi
authors.affiliation: a Molecular Biology and Genetics Unit , Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bangalore , India.|b Neuroscience Unit , Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bangalore , India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Manjithaya
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D020267:MPTP Poisoning / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010091:Oximes / Q000494:pharmacology* / Q000627:therapeutic use; D066263:Protein Aggregation, Pathological / Q000188:drug therapy; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: C483321:6-bromoindirubin-3'-oxime; D007211:Indoles; D018696:Neuroprotective Agents; D010091:Oximes; D051844:alpha-Synuclein; D000071679:Glycogen Synthase Kinase 3 beta
keywords: 6-Bio; MPTP; TH; autolysosomes; autophagy; high-throughput screening; neurodegeneration, SNCA