BACE1 inhibitors: Attractive therapeutics for alzheimer's disease

Boris Decourt, Mi Mi Macias, Marwan Sabbagh, Abdu Adem

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

One of the neuropathological hallmarks of Alzheimer's disease (AD) is the presence of brain senile plaques made up principally of aggregated amyloid beta (Aβ) peptides. Aβ is produced during the consecutive proteolysis of the transmembrane amyloid precursor protein (APP) by β- and γ-secretases. Genetic and pharmacological manipulations have demonstrated the major β -secretase in AD that makes the initial cleavage required for synthesis of Aβ is the beta-site APP-cleaving enzyme 1 (BACE1). It is therefore very tempting to consider inhibiting BACE1 as a potential AD therapeutic intervention. Here, we review the current knowledge and the molecular and physiological challenges associated with BACE1 inhibition. We also propose alternatives to the direct targeting of CNS BACE1 to prevent AD, as well as methods to measure the therapeutic efficacy of BACE1 inhibition.

Original languageEnglish (US)
Title of host publicationDrug Design and Discovery in Alzheimer's Disease
PublisherElsevier Inc.
Pages518-546
Number of pages29
ISBN (Electronic)9780128039595
ISBN (Print)9780128039595
DOIs
StatePublished - Jan 1 2014

Keywords

  • APP
  • Alzheimer's
  • Amyloid
  • BACE1
  • Bapineuzumab
  • Beta-secretase
  • Blood brain barrier
  • Central nervous system
  • Clinical trial
  • Design
  • Down syndrome
  • Gamma-secretase
  • Immunotherapy
  • Inhibition
  • Modulation
  • Optimization
  • Peptidomimetic
  • Periphery
  • Solanezumab
  • Trafficking

ASJC Scopus subject areas

  • Chemistry(all)

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  • Cite this

    Decourt, B., Macias, M. M., Sabbagh, M., & Adem, A. (2014). BACE1 inhibitors: Attractive therapeutics for alzheimer's disease. In Drug Design and Discovery in Alzheimer's Disease (pp. 518-546). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-803959-5.50010-6