Ad的元兇之一γ-Secretase是Presenilins
disease的元兇之一是γ-secretase,最近幾篇在Nature,NCB,PNAS上的文章通過充分的證據(jù)可以將γ-secretase緝拿歸案了,他就是蛋白酶-presenilins。
γ-secretase引起人們很大興趣的原因是他們與AD的特征之一-淀粉斑的形成有關(guān)。淀粉斑的主要組成是β淀粉樣蛋白,β淀粉樣蛋白分兩類,Aβ40,Aβ42,分別由β-secretase和γ-secretase切分。β-secretase去年末已被證實是膜結(jié)合的天冬氨酰蛋白酶。通過這幾個小組的工作,將γ-secretase確定為presenilin-1、-2。
將AD的元兇確定后,接下來的研究可以集中在這些蛋白酶究竟如何引發(fā)AD及研究相應(yīng)的藥物上了。
相關(guān)文章:
Li, Y.-M. et al. Photoactivated g-secretase inhibitors
directed to the active site covalently label presenilin-1. Nature 405,689–694 (2000).
Esler, W. P. et al. Transition-state analogue
inhibitors of g-secretase bind directly to presenilin-1. Nature Cell
Biology 2, 428–434 (2000).
Li, Y.-M. et al. Presenilin-1 is linked with g-secretase activity in the detergent solubilized state. Proc. Natl Acad. Sci USA
97, 6138–6143 (2000).
Review
Wolfe, M. S., De Los Angeles, J., Miller, D. D., Xia,W. & Selkoe, D. J. Are presenilins intramembrane-cleaving
proteases? Implications for the molecular mechanism of Alzheimer's disease. Biochemistry 38, 11223–11230 (1999).
News and Views
De Strooper, B. Closing in on g-secretase. Nature 405,627–629 (2000).
Further reading
Selkoe, D. J. & Wolfe, M. S. In search of g-secretase: presenilin at the cutting edge. Proc. Natl Acad. Sci. USA 97,5690–5692 (2000).
新思路
新技術(shù)—其他文章, 百拇醫(yī)藥
γ-secretase引起人們很大興趣的原因是他們與AD的特征之一-淀粉斑的形成有關(guān)。淀粉斑的主要組成是β淀粉樣蛋白,β淀粉樣蛋白分兩類,Aβ40,Aβ42,分別由β-secretase和γ-secretase切分。β-secretase去年末已被證實是膜結(jié)合的天冬氨酰蛋白酶。通過這幾個小組的工作,將γ-secretase確定為presenilin-1、-2。
將AD的元兇確定后,接下來的研究可以集中在這些蛋白酶究竟如何引發(fā)AD及研究相應(yīng)的藥物上了。
相關(guān)文章:
Li, Y.-M. et al. Photoactivated g-secretase inhibitors
directed to the active site covalently label presenilin-1. Nature 405,689–694 (2000).
Esler, W. P. et al. Transition-state analogue
inhibitors of g-secretase bind directly to presenilin-1. Nature Cell
Biology 2, 428–434 (2000).
Li, Y.-M. et al. Presenilin-1 is linked with g-secretase activity in the detergent solubilized state. Proc. Natl Acad. Sci USA
97, 6138–6143 (2000).
Review
Wolfe, M. S., De Los Angeles, J., Miller, D. D., Xia,W. & Selkoe, D. J. Are presenilins intramembrane-cleaving
proteases? Implications for the molecular mechanism of Alzheimer's disease. Biochemistry 38, 11223–11230 (1999).
News and Views
De Strooper, B. Closing in on g-secretase. Nature 405,627–629 (2000).
Further reading
Selkoe, D. J. & Wolfe, M. S. In search of g-secretase: presenilin at the cutting edge. Proc. Natl Acad. Sci. USA 97,5690–5692 (2000).
新思路
新技術(shù)—其他文章, 百拇醫(yī)藥
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