Ad的元凶之一γ-Secretase是Presenilins
disease的元凶之一是γ-secretase，最近几篇在Nature,NCB,PNAS上的文章通过充分的证据可以将γ-secretase缉拿归案了，他就是蛋白酶－presenilins。
γ-secretase引起人们很大兴趣的原因是他们与AD的特征之一－淀粉斑的形成有关。淀粉斑的主要组成是β淀粉样蛋白，β淀粉样蛋白分两类，Aβ40,Aβ42,分别由β-secretase和γ-secretase切分。β-secretase去年末已被证实是膜结合的天冬氨酰蛋白酶。通过这几个小组的工作，将γ-secretase确定为presenilin-1、-2。
将AD的元凶确定后，接下来的研究可以集中在这些蛋白酶究竟如何引发AD及研究相应的药物上了。
相关文章：
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
新技术—其他文章, 百拇医药
γ-secretase引起人们很大兴趣的原因是他们与AD的特征之一－淀粉斑的形成有关。淀粉斑的主要组成是β淀粉样蛋白，β淀粉样蛋白分两类，Aβ40,Aβ42,分别由β-secretase和γ-secretase切分。β-secretase去年末已被证实是膜结合的天冬氨酰蛋白酶。通过这几个小组的工作，将γ-secretase确定为presenilin-1、-2。
将AD的元凶确定后，接下来的研究可以集中在这些蛋白酶究竟如何引发AD及研究相应的药物上了。
相关文章：
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
新技术—其他文章, 百拇医药