Regulation of β-site APP-cleaving enzyme 1 gene expression and its role in Alzheimer's disease

J Neurochem. 2012 Jan;120 Suppl 1:62-70. doi: 10.1111/j.1471-4159.2011.07515.x. Epub 2011 Nov 28.

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder leading to dementia. Neuritic plaques are the hallmark neuropathology in AD brains. Proteolytic processing of amyloid-β precursor protein at the β site by beta-site amyloid-β precursor protein-cleaving enzyme 1 (BACE1) is essential to generate Aβ, a central component of the neuritic plaques. BACE1 is increased in some sporadic AD brains, and dysregulation of BACE1 gene expression plays an important role in AD pathogenesis. This review will focus on the regulation of BACE1 gene expression at the transcriptional, post-transcriptional, translation initiation, translational and post-translational levels, and its role in AD pathogenesis. Further studies on BACE1 gene expression regulation will greatly contribute to our understanding of AD pathogenesis and reveal potential novel approaches for AD prevention and drug development.

Publication types

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

MeSH terms

  • Alzheimer Disease / enzymology*
  • Alzheimer Disease / etiology*
  • Alzheimer Disease / genetics
  • Amyloid Precursor Protein Secretases / biosynthesis
  • Amyloid Precursor Protein Secretases / genetics*
  • Amyloid Precursor Protein Secretases / physiology
  • Amyloid beta-Protein Precursor / chemistry*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Aspartic Acid Endopeptidases / biosynthesis
  • Aspartic Acid Endopeptidases / genetics*
  • Aspartic Acid Endopeptidases / physiology
  • Gene Expression Regulation, Enzymologic / physiology*
  • Humans
  • Plaque, Amyloid / enzymology*
  • Plaque, Amyloid / pathology
  • Protein Processing, Post-Translational / genetics

Substances

  • Amyloid beta-Protein Precursor
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human