Modulation of γ- and β-Secretases as Early Prevention Against Alzheimer's Disease

Biol Psychiatry. 2018 Feb 15;83(4):320-327. doi: 10.1016/j.biopsych.2017.08.001. Epub 2017 Aug 10.

Abstract

The genetic evidence implicating amyloid-β in the initial stage of Alzheimer's disease is unequivocal. However, the long biochemical and cellular prodromal phases of the disease suggest that dementia is the result of a series of molecular and cellular cascades whose nature and connections remain unknown. Therefore, it is unlikely that treatments directed at amyloid-β will have major clinical effects in the later stages of the disease. We discuss the two major candidate therapeutic targets to lower amyloid-β in a preventive mode, i.e., γ- and β-secretase; the rationale behind these two targets; and the current state of the field.

Keywords: Alzheimer; Amyloid-β; Prevention; Therapy; β-Secretase; γ-Secretase.

Publication types

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

MeSH terms

  • Alzheimer Disease / enzymology
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / prevention & control
  • Alzheimer Disease / therapy*
  • Amyloid Precursor Protein Secretases / drug effects*
  • Amyloid Precursor Protein Secretases / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Humans

Substances

  • Amyloid beta-Peptides
  • Amyloid Precursor Protein Secretases