期刊
JOURNAL OF NEUROCHEMISTRY
卷 120, 期 -, 页码 9-21出版社
WILEY
DOI: 10.1111/j.1471-4159.2011.07519.x
关键词
a-secretase; ss-amyloid precursor protein; ss-secretase; -secretase; caspase
资金
- National Institutes of Health [R01AG021173, R01NS046673, R01AG030197, R03AG034366]
- Alzheimer's Association
- American Health Assistance Foundation
- National Natural Science Foundation of China [30973150]
- 973 Prophase Project [2010CB535004]
- Natural Science Funds for Distinguished Young Scholar of Fujian Province [2009J06022]
- Program for New Century Excellent Talents in Universities (NCET)
- Fundamental Research Funds for the Central Universities
- Fok Ying Tung Education Foundation
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS046673] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG030197, R03AG034366, R01AG021173] Funding Source: NIH RePORTER
beta-Amyloid precursor protein (APP) is a critical factor in the pathogenesis of Alzheimers disease (AD). APP undergoes post-translational proteolysis/processing to generate the hydrophobic beta-amyloid (A beta) peptides. Deposition of A beta in the brain, forming oligomeric A beta and plaques, is identified as one of the key pathological hallmarks of AD. The processing of APP to generate A beta is executed by beta- and gamma-secretase and is highly regulated. A beta toxicity can lead to synaptic dysfunction, neuronal cell death, impaired learning/memory and abnormal behaviors in AD models in vitro and in vivo. Aside from A beta, proteolytic cleavages of APP can also give rise to the APP intracellular domain, reportedly involved in multiple types of cellular events such as gene transcription and apoptotic cell death. In addition to amyloidogenic processing, APP can also be cleaved by a-secretase to form a soluble or secreted APP ectodomain (sAPP-alpha) that has been shown to be mostly neuro-protective. In this review, we describe the mechanisms involved in APP metabolism and the likely functions of its various proteolytic products to give a better understanding of the patho/physiological functions of APP.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据