★	第81回支援センターセミナーを共催しました。	・
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■ 日　時：　平成２３年３月１５日（火）１６：００ ～ ■ 場　所：　基礎研究棟２階　教職員ロビー ■ 演　題：　アルツハイマー病および外傷性脳損傷の治療標的としてのガンマセクレターゼ 　　　　　- Gamma-secretase, a therapeutic target for Alzheimer's disease 　　　　　　and traumatic brain injury - ■ 演　者：　松岡　康治（Yasuji Matsuoka, Ph.D.） 　　　　　　　　グラクソスミスクライン・シンガポール研究所マネージャー 　　　　　　　　(Manager, Neural Pathway Discovery, GlaxoSmithKline, Singapore) 　　　　　　　　ジョージタウン大学メディカルセンター神経内科学特任准教授 　　　　　　　　(Adjunct Associate Professor of Neurology, Georgetown 　　　　　　　　University Medical Center) 実験実習支援センター福堀先生より開催の挨拶 遠山　育夫教授による松岡先生の紹介   松岡　康治先生によるセミナー 左から京都薬科大学北村准教授、松岡先生、遠山先生 　 ＜講演要旨＞ 　　Gamma-secretase is a key enzyme in generation of amyloid beta (Ab) and accumulation of Ab is a pathological hallmark of Alzheimer's disease (AD). Therefore, inhibition of g-secretase is a potential therapeutic target. Gamma-secretase has many (>40) substrates in addition to Ab precursor protein. Since some substrates, such as Notch, is a critical in physiological system, presumably, substrate selectivity is critical to gain desired safety profile. First generation g-secretase inhibitors (GSIs) have only limited (if there is any) substrate selectivity, and also induced paradoxical increase of Ab after transientreduction (Ab-rebound) in pre-clinical species and human. We investigated mechanism of Ab-rebound using GSI and g-secretase modulators (GSMs) which shift cleavage site and maintain cleavage of substrates. We found that an accumulation of g-secretase substrates is one of causes of GSI-mediated Ab-rebound. In combination of substrate selectivity, GSMs may be more useful Ab-lowering approach for treatment AD.     Acute and transient increase of Ab is seen after traumatic brain injury in pre-clinical species and human. We hypothesized overproduction of Ab is one of causes of neurodegeneration and tested impact of Ab-lowering approach using GSI. Treatment with a GSI significantly reduced neurodegeneration and improved dysfunction. GSI and other Ab-lowering agents may be useful for treatment of traumatic brain injury. 参考文献 Loane, D.J., Pocivavsek, A., Moussa, C. E-H., Thompson, R., Matsuoka, Y., Faden, A.I., Rebeck, G.W., Burns, M.P. (2009) APP secretases as therapeutic targets for traumatic brain injury. Nature Medicine, 15: 377-379.