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

作者:Suresh S N; Chavalmane Aravinda K; Vidyadhara D J; Yarreiphang Haorei; Rai Shashank; Paul Abhik; Clement James P; Alladi Phalguni Anand; Manjithaya Ravi
来源:Autophagy, 2017, 13(7): 1221-1234.
DOI:10.1080/15548627.2017.1302045

摘要

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/alpha-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.

  • 出版日期2017
  • 单位南阳理工学院