a Molecular Biology and Genetics Unit , Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bangalore , India.
c Department of Neurophysiology , National Institute of Mental Health and Neuro Sciences , Bangalore , India.
Autophagy. 2017 Jul 3;13(7):1221-1234. doi: 10.1080/15548627.2017.1302045. Epub 2017 Mar 28.
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.
帕金森病（PD）是一种危及生命的神经退行性运动障碍，目前尚无有效的治疗干预措施。我们已经确定了一种小分子自噬调节剂 6-Bio，它可以清除酵母和哺乳动物细胞系中有毒的 SNCA/α-突触核蛋白（一种与突触核蛋白病有关的蛋白质）聚集体。6-Bio 诱导自噬，并显著增强自噬溶酶体的形成，导致 SNCA 降解。重要的是，6-Bio 的神经保护功能通过帕金森病的临床前模型中的免疫组织化学和行为分析来设想，其中它在小鼠中脑的多巴胺能（DAergic）神经元中诱导自噬，以清除有毒的蛋白质聚集体，这表明它可能是一种治疗蛋白质构象紊乱的潜在候选药物。
