創薬科学部門＜連携講座＞Translational Pharmaceutical Sciences[Research]The Uehara laboratory focuses on the elucidation of the molecular mechanisms of neurodegenerative diseases, such as Parkinson’s/Alzheimer’s diseases and brain ischemia. We are specifically interested in the regulatory system of signaling pathways that play a central role in the responses triggered by oxidative/nitrosative stress. Among the laboratory's accomplishments and ongoing activities are (1) the isolation and characterization of S-nitrosylated or oxidized proteins by several screening techniques; (2) investigation of the intracellular signaling in response to oxidative/nitrosative stress; (3) elucidation of the molecular mechanisms of endoplasmic reticulum (ER) stress (Unfolded Protein Response) in neuronal cells/ brain; (4) discovery of substrate proteins to E3 ligases involved in ER-associated degradation (ERAD); and (5) drug discovery based on original results published. These studies are expected to lead to the emergence of new strategies for the development of neuroprotective drugs with pharmacological techniques. 酸化ストレスの中、とくに一酸化窒素（NO）が介在するニトロソ化ストレスによる病態生理機構を中心に研究しています。これまでに多くのNO標的タンパク質の同定に成功し、その酸化修飾が及ぼす影響や生理的/病態生理的役割について証明してきました。最近では、NO修飾を特異的に阻害する化合物の開発に成功し、薬理学的手法からその 有用性を検証しています。また、NOと同様あるいは類似の性質を有する外来性化学物質の作用に関しても調べており、環境物質が及ぼす人体への影響についても解析しています。自分たちの実験から得た成果を応用して、「新規診断法」の開発や「シーズ化合物」の探索を手がけています。教 授 上原 孝［博士（薬学）］Professor Takashi Uehara, Ph. D.分野連絡先分野連絡先2. Nakahara K et al. (2021) Covalent N-arylation by the pollutant 1,2-naphthoquinone activates the EGF receptor. J. Biol. Chem. 296:100524. doi: 10.1016/j.jbc.2021.1005243. Hiraoka H et al. (2021) Spatiotemporal analysis of the UPR transition induced by methylmercury in the mouse brain. Arch. Toxicol. 95(4):1241-1250.4. Numajiri N et al . (2011) On-off system for PI3-kinase-Akt signaling through S-nitrosylation of PTEN. Proc. Natl. Acad. Sci. USA 108, 10349-10354.5. Uehara T et al. (2006) S-nitrosylated protein-disulfi d e isomerase links protein misfolding to neurodegeneration. Nature 441, 513-517.【代表論文】1. Okuda K et al. (2023) Pivotal role for S-nitrosylation of DNA methyltransferase 3B in epigenic regulation of tumorigenesis. Nature Communications 14(1):621.上原 孝（Takashi Uehara）上原 孝（Takashi Uehara）［岡山大学学術研究院医歯薬学域薬効解析学分野］TEL&FAX ：（薬）086-2511-7939E-mail：uehara-t@okayama-u.ac.jpURL：http://www.okayama-u.ac.jp/user/yakko/教 授 上原 孝Prof. Uehara36創薬産学官連携講座１
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