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Trends Pharmacol Sci. 2013 Apr;34(4):215-25. doi: 10.1016/j.tips.2013.01.008. Epub 2013 Feb 27.

β-Secretase: its biology as a therapeutic target in diseases.

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1
Center for Advanced Therapeutic Strategies for Brain Disorders, Roskamp Institute, Sarasota, FL 34203, USA.

Abstract

β-Secretase (BACE1, β-site APP cleaving enzyme 1) is an aspartic proteinase that has multiple functions in various physiological processes, such as cell differentiation, immunoregulation, and cell death. There is increasing evidence that changes in BACE1 activity are involved in many diseases, such as Alzheimer's disease (AD), schizophrenia, epileptic behavior, and others. However, a deeper understanding of the molecular biology of BACE1 is necessary for further exploration of cell development, immunological regulation, and disease pathogenesis. Here, we review the molecular and cellular biology of BACE1, including its enzymatic properties, structure, biosynthesis, and physiological functions to provide a new perspective and rational assessment of drugability. Lastly, we discuss proposed strategies to control BACE1 activity for possible therapeutic application.

PMID:
23452816
PMCID:
PMC3691103
DOI:
10.1016/j.tips.2013.01.008
[Indexed for MEDLINE]
Free PMC Article
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