期刊
JOURNAL OF NEUROCHEMISTRY
卷 120, 期 -, 页码 34-45出版社
WILEY
DOI: 10.1111/j.1471-4159.2011.07477.x
关键词
a-secretase; ADAM proteases; Alzheimer's disease; APP
Absract Secretase is a generic term coined more than 20 years ago to refer to a group of proteases responsible for the cleavage of a vast number of membrane proteins. These endoproteolytic events result in the extracellular or intracellular release of soluble metabolites associated with a broad range of intrinsic physiological functions. a-Secretase refers to the activity targeting the amyloid precursor protein (APP) and generating sAPPa, a soluble extracellular fragment potentially associated with neurotrophic and neuroprotective functions. Several proteases from the a disintegrin and metalloproteinase (ADAM) family, including ADAM10 and ADAM17, have been directly or indirectly associated with the constitutive and regulated a-secretase activities. Recent evidence in primary neuronal cultures indicates that ADAM10 may represent the genuine constitutive a-secretase. Mainly because a-secretase cleaves APP within the sequence of A beta, the core component of the cerebral amyloid plaques in Alzheimers disease, a-secretase activation is considered to be of therapeutic value. In this article, we will provide a historical perspective on the characterization of a-secretase and review the recent literature on the identification and biology of the current a-secretase candidates.
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