Selectivity to amyloid-β precursor protein cleavage provides hope against Alzheimer's

被引：0
作者：
Taisuke Tomita
Philip C Wong
机构：
[1] Graduate School of Pharmaceutical Science,Department of Neuropathology and Neuroscience
[2] The University of Tokyo,Departments of Pathology and Neuroscience
[3] The Johns Hopkins University School of Medicine,undefined
来源：
Alzheimer's Research & Therapy | / 3卷
关键词：
Notch Signaling; Notch Target Gene; Skin Cancer Risk; Elan Pharmaceutical; Strong Experimental Support;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Toward development of a safe and effective treatment for Alzheimer's disease, Elan Pharmaceuticals reported a novel γ-secretase inhibitor that specifically targets the cleavage of amyloid-β precursor protein, opening the way to design of substrate-specific γ-secretase inhibitors that would reduce the amyloid burden without significant adverse events.
引用
收藏
相关论文
共 161 条
  • [1] De Strooper B(2010)The secretases: enzymes with therapeutic potential in Alzheimer disease Nat Rev Neurol 6 99-107
  • [2] Vassar R(2010)Alzheimer's failure raises questions about disease-modifying strategies Nat Rev Drug Discov 9 749-751
  • [3] Golde T(2009)The canonical Notch signaling pathway: unfolding the activation mechanism Cell 137 216-233
  • [4] Extance A(2007)γ-secretase attenuates amyloid burden and limits mechanism-based liabilities J Neurosci 27 10849-10859
  • [5] Kopan R(2003)Notch1 functions as a tumor suppressor in mouse skin Nat Genet 33 416-421
  • [6] Ilagan MX(2011)Therapeutic intervention for Alzheimer's disease with γ-secretase inhibitors: still a viable option? Expert Opin Investig Drugs 20 325-341
  • [7] Li T(2010)Amyloid precursor protein selective gamma-secretase inhibitors for treatment of Alzheimer's disease Alzheimers Res Ther 2 36-2938
  • [8] Wen H(2010)Substrate docking to γ-secretase allows access of γ-secretase modulators to an allosteric site Nat Commun 1 130-260
  • [9] Brayton C(2008)Identification of γ-secretase inhibitor potency determinants on presenilin J Biol Chem 283 2927-98
  • [10] Laird FM(2010)Novel research horizons for presenilins and gamma-secretases in cell biology and disease Annu Rev Cell Dev Biol 26 235-158
12345678910