Regulation of neuronal ageing through the mTOR signaling by acetylation

2017 Fiscal Year Final Research Report

• Project/Area Number: 26430072
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokai Gakuin University (2015-2017); Nagasaki University (2014)
• Principal Investigator: YASUDA KUNIHIKO 東海学院大学, 健康福祉学部, 准教授(移行) (50278446)
• Co-Investigator(Renkei-kenkyūsha): NAGATA Kazuhiro 京都産業大学, 総合生命科学部 生命システム学科, 客員教授 (50127114) ; OHYAMA Kyoji 東京医科大学, 大学院医学研究科, 准教授 (00255423)
• Research Collaborator: NAKAYAMA Yuji 京都薬科大学, 薬学部, 教授 (10280918) ; SAITO Yohei 京都薬科大学, 薬学部, 助教 (90411032) ; MORI Nozomu 長崎大学, 医歯薬学総合研究科, 教授 (00130394)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 神経老化 / HDAC6 / Mdm20 / 分子シャペロン / オートファジー / mTOR / Akt / アセチル化修飾

Outline of Final Research Achievements

Akt/PKA (A kinase) is one of key molecules in insulin signaling, functions in various critical steps in signal transduction for maintaining cellular homeostasis, leading to cell survival and /or longevity. The Akt activity regulates through the phosphorylation by PDK1, under the insulin signaling, and mTORC2/PDK2. Interestingly, in this research, we identified HDAC6 (histone deacetylase) and Mdm20 (an auxiliary subunit of NatB) as the novel regulators of Akt activity. Furthermore, we found that Mdm20 regulates the expression levels of Rictor, one of components of mTORC2 and HDAC6 regulates interaction with each components of mTORC1 and mTORC2. These acetyl-related molecules break through the concept of acetyl modification function in cytoplasm and simultaneously hold promise for the effect of anti-ageing through the regulation of Akt activity under the insulin signaling by in the future.

Free Research Field

生化学・分子生物学・細胞生物学