Targeting the β secretase BACE1 for Alzheimer's disease therapy

Riqiang Yan, Robert Vassar*

*Corresponding author for this work

Research output: Contribution to journalReview article

365 Scopus citations

Abstract

The β secretase, widely known as β-site amyloid precursor protein cleaving enzyme 1 (BACE1), initiates the production of the toxic amyloid β (Aβ) that plays a crucial early part in Alzheimer's disease pathogenesis. BACE1 is a prime therapeutic target for lowering cerebral Aβ concentrations in Alzheimer's disease, and clinical development of BACE1 inhibitors is being intensely pursued. Although BACE1 inhibitor drug development has proven challenging, several promising BACE1 inhibitors have recently entered human clinical trials. The safety and efficacy of these drugs are being tested at present in healthy individuals and patients with Alzheimer's disease, and will soon be tested in individuals with presymptomatic Alzheimer's disease. Although hopes are high that BACE1 inhibitors might be efficacious for the prevention or treatment of Alzheimer's disease, concerns have been raised about potential mechanism-based side-effects of these drugs. The potential of therapeutic BACE1 inhibition might prove to be a watershed in the treatment of Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)319-329
Number of pages11
JournalThe Lancet Neurology
Volume13
Issue number3
DOIs
StatePublished - Mar 2014

ASJC Scopus subject areas

  • Clinical Neurology

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