Amyloid precursor protein processing and Alzheimer's disease.
Amyloid precursor protein processing and Alzheimer's disease.
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DOI：
10.1146/annurev-neuro-061010-113613
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发表时间：
2011
影响因子：
13.9
通讯作者：
Wong PC
中科院分区：
文献类型：
--
作者：
O'Brien RJ;Wong PC
阿尔茨海默病（AD）是世界范围内痴呆症的主要原因，其特征是β-淀粉样肽（Aβ）在大脑内的积累以及微管相关蛋白tau的过度磷酸化和断裂形式。遗传、生化和行为研究表明，序次淀粉样前体蛋白（APP）蛋白水解生理性产生神经毒性Aβ肽是AD发展的关键步骤。APP是一种单遍跨膜蛋白，在大脑中高水平表达，并通过一系列连续的蛋白酶以快速和高度复杂的方式代谢，包括膜内γ-分泌酶复合物，该复合物还处理其他关键调节分子。为什么Aβ在老年人大脑中积累尚不清楚，但可能与APP代谢或Aβ消除的变化有关。从APP加工的生化和遗传学研究中获得的经验教训将对开发治疗AD的治疗靶点至关重要。
Alzheimer’s disease (AD), the leading cause of dementia worldwide, is characterized by the accumulation of the β-amyloid peptide (Aβ) within the brain along with hyperphosphorylated and cleaved forms of the microtubule-associated protein tau. Genetic, biochemical, and behavioral research suggest that physiologic generation of the neurotoxic Aβ peptide from sequential amyloid precursor protein (APP) proteolysis is the crucial step in the development of AD. APP is a single-pass transmembrane protein expressed at high levels in the brain and metabolized in a rapid and highly complex fashion by a series of sequential proteases, including the intramembranous γ-secretase complex, which also process other key regulatory molecules. Why Aβ accumulates in the brains of elderly individuals is unclear but could relate to changes in APP metabolism or Aβ elimination. Lessons learned from biochemical and genetic studies of APP processing will be crucial to the development of therapeutic targets to treat AD.
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影响因子：
12.3
作者：
Avramopoulos D
通讯作者：
Avramopoulos D
影响因子：
14
作者：
Brookmeyer, Ron;Johnson, Elizabeth;Arrighi, H. Michael
通讯作者：
Arrighi, H. Michael
影响因子：
64.8
作者：
Chen, GQ;Chen, KS;Morris, RGM
通讯作者：
Morris, RGM
DOI：
10.1073/pnas.0503689102
发表时间：
2005-09-20
影响因子：
11.1
作者：
Andersen, OM;Reiche, J;Willnow, TE
通讯作者：
Willnow, TE
影响因子：
82.9
作者：
Bateman, Randall J.;Munsell, Ling Y.;Holtzman, David M.
通讯作者：
Holtzman, David M.