In:
Journal of Neurochemistry, Wiley, Vol. 130, No. 1 ( 2014-07), p. 4-28
Abstract:
The β‐site APP cleaving enzymes 1 and 2 ( BACE 1 and BACE 2) were initially identified as transmembrane aspartyl proteases cleaving the amyloid precursor protein ( APP ). BACE 1 is a major drug target for Alzheimer's disease because BACE 1‐mediated cleavage of APP is the first step in the generation of the pathogenic amyloid‐β peptides. BACE 1, which is highly expressed in the nervous system, is also required for myelination by cleaving neuregulin 1. Several recent proteomic and in vivo studies using BACE 1‐ and BACE 2‐deficient mice demonstrate a much wider range of physiological substrates and functions for both proteases within and outside of the nervous system. For BACE 1 this includes axon guidance, neurogenesis, muscle spindle formation, and neuronal network functions, whereas BACE 2 was shown to be involved in pigmentation and pancreatic β‐cell function. This review highlights the recent progress in understanding cell biology, substrates, and functions of BACE proteases and discusses the therapeutic options and potential mechanism‐based liabilities, in particular for BACE inhibitors in Alzheimer's disease. image The protease BACE1 is a major drug target in Alzheimer disease. Together with its homolog BACE2, both proteases have an increasing number of functions within and outside of the nervous system. This review highlights recent progress in understanding cell biology, substrates, and functions of BACE proteases and discusses the therapeutic options and potential mechanism‐based liabilities, in particular for BACE inhibitors in Alzheimer disease.
Type of Medium:
Online Resource
ISSN:
0022-3042
,
1471-4159
DOI:
10.1111/jnc.2014.130.issue-1
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2020528-4
SSG:
12
