期刊
FRONTIERS IN MOLECULAR NEUROSCIENCE
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2017.00097
关键词
Alzheimer's disease; amyloid plaques; amyloid precursor protein; secretase; BACE1; BACE2; aspartic protease; BACE substrates
资金
- National Institutes of Health [NS074256, AG025493, AG046929, NM103942]
- National Multiple Sclerosis Society [RG 4012A1/1]
BACE1 was discovered as the beta-secretase for initiating the cleavage of amyloid precursor protein (APP) at the beta-secretase site, while its close homology BACE2 cleaves APP within the beta-amyloid (A beta) domain region and shows distinct cleavage preferences in vivo. Inhibition of BACE1 proteolytic activity has been confirmed to decrease A b generation and amyloid deposition, and thus specific inhibition of BACE1 by small molecules is a current focus for Alzheimer's disease therapy. While BACE1 inhibitors are being tested in advanced clinical trials, knowledge regarding the properties and physiological functions of BACE is highly important and this review summarizes advancements in BACE1 research over the past several years. We and others have shown that BACE1 is not only a critical enzyme for testing the Amyloid Hypothesis associated with Alzheimer's pathogenesis, but also important for various functions such as axon growth and pathfinding, astrogenesis, neurogenesis, hyperexcitation, and synaptic plasticity. BACE2 appears to play different roles such as glucose homeostasis and pigmentation. This knowledge regarding BACE1 functions is critical for monitoring the safe use of BACE1 inhibitors in humans.
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