The leukotriene signaling pathway: a druggable target in Alzheimer's disease

Drug Discov Today. 2019 Feb;24(2):505-516. doi: 10.1016/j.drudis.2018.09.008. Epub 2018 Sep 18.

Abstract

The underlying pathology of Alzheimer's disease (AD) is complex and includes, besides amyloid beta (Aβ) plaque depositions and neurofibrillary tangles, brain atrophy and neurodegeneration, neuroinflammation, impaired neurogenesis, vascular and blood-brain barrier (BBB) disruptions, neurotransmitter disbalances, and others. Here, we hypothesize that such complex pathologies can only be targeted efficiently through pleiotropic approaches. One interesting drug target is the leukotriene pathway, which mediates various aspects of AD pathology. Approaching this pathway at different levels with genetic and pharmacological tools demonstrated beneficial outcomes in several in vivo studies using different mouse models of AD. Here, we review the current literature on the leukotriene signaling pathway as a target for drug development in AD.

Publication types

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

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / therapy
  • Animals
  • Blood-Brain Barrier / metabolism
  • Cell Death
  • Drug Repositioning
  • Humans
  • Leukotrienes / metabolism*
  • Neurogenesis
  • Neurons / metabolism
  • Signal Transduction

Substances

  • Leukotrienes