The basic biology of BACE1: A key therapeutic target for Alzheimer's disease

S. L. Cole, R. Vassar*

*Corresponding author for this work

Research output: Contribution to journalReview article

51 Scopus citations

Abstract

Alzheimer's disease (AD) is an intractable, neurodegenerative disease that appears to be brought about by both genetic and non-genetic factors. The neuropathology associated with AD is complex, although amyloid plaques composed of the β-amyloid peptide (Aβ) are hallmark neuropathological lesions of AD brain. Indeed, Aβ plays an early and central role in this disease. β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the initiating enzyme in Aβ genesis and BACE1 levels are elevated under a variety of conditions. Given the strong correlation between Aβ and AD, and the elevation of BACE1 in this disease, this enzyme is a prime drug target for inhibiting Aβ production in AD. However, nine years on from the initial identification of BACE1, and despite intense research, a number of key questions regarding BACE1 remain unanswered. Indeed, drug discovery and development for AD continues to be challenging. While current AD therapies temporarily slow cognitive decline, treatments that address the underlying pathologic mechanisms of AD are completely lacking. Here we review the basic biology of BACE1. We pay special attention to recent research that has provided some answers to questions such as those involving the identification of novel BACE1 substrates, the potential causes of BACE1 elevation and the putative function of BACE1 in health and disease. Our increasing understanding of BACE1 biology should aid the development of compounds that interfere with BACE1 expression and activity and may lead to the generation of novel therapeutics for AD.

Original languageEnglish (US)
Pages (from-to)509-530
Number of pages22
JournalCurrent Genomics
Volume8
Issue number8
DOIs
StatePublished - Dec 1 2007

Keywords

  • Alzheimer's
  • BACE1
  • Regulation
  • Stress
  • Vascular disease
  • β-secretase

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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