Creation of neurodegenerative model due to mitochondrial reactive oxygen species and identification of novel disease molecules

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K21261
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy; General pharmacology
• Research Institution: Fukushima Medical University
• Principal Investigator: OGURA MASATO 福島県立医科大学, 医学部, 助教 (10548978)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 活性酸素種 / ミトコンドリア / プロテオーム / アポトーシス / シグナル伝達 / 神経細胞 / 神経変性疾患 / 質量分析

Outline of Final Research Achievements

Reactive oxygen species (ROS) are implicated in the modulation of diverse processes including neuronal death. To evaluate the effects of metabolic ROS produced by mitochondria on neurodegeneration, we created transgenic (Tg) mice expressing a phosphorylation-defective mutant of succinate dehydrogenase A in neurons (nSDHAY215F). Neurons in substantia nigra of in male nSDHAY215F mice produced three times more ROS than those in control mice, and increased both the activated caspase-3 and the TUNEL reactivity. The nSDHAY215F mice further displayed increased JNK cascade in neurons of substantia nigra. We identified several factors from the nSDHAY215F mice as a mitochondrial ROS signal that associate with JNK cascade and neuronal death. These results suggest that mitochondrial ROS may directly regulate neuronal survival in substantia nigra through modulation of JNK cascade. Exact molecular targets for mitochondrial ROS will be discussed.

Free Research Field

薬理学