Understanding BACE1: essential protease for amyloid-beta production in Alzheimer's disease

Cell Mol Life Sci. 2008 Oct;65(20):3265-89. doi: 10.1007/s00018-008-8271-3.


The identification of the aspartic protease BACE1 (beta-secretase) was a defining event in research aimed at understanding the molecular mechanisms that underlie Alzheimer's disease (AD) pathogenesis. This is because BACE1 catalyses the rate limiting step in the production of amyloid-beta (Abeta) the principal component of plaque pathology in AD, the excessive production of which is believed to be a primary cause of neurodegeneration, and cognitive dysfunction in AD. Subsequent discoveries showed that genetic deletion of BACE1 completely abolishes Abeta production and deposition in vivo, and that BACE1 activity is significantly increased in AD brain. In this review we present current knowledge on BACE1, discussing its structure, function and complex regulation with a view to understanding BACE1 function in the brain, and BACE1 as a target in blocking aberrant Abeta production in AD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / enzymology*
  • Amino Acid Sequence
  • Amyloid Precursor Protein Secretases / chemistry
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid Precursor Protein Secretases / metabolism*
  • Amyloid beta-Peptides / biosynthesis*
  • Animals
  • Evolution, Molecular
  • Humans
  • Molecular Sequence Data
  • Protein Processing, Post-Translational
  • Substrate Specificity


  • Amyloid beta-Peptides
  • Amyloid Precursor Protein Secretases