Microglial inflammation and phagocytosis in Alzheimer's disease: Potential therapeutic targets

Br J Pharmacol. 2019 Sep;176(18):3515-3532. doi: 10.1111/bph.14618. Epub 2019 May 11.

Abstract

One of the largest unmet medical needs is a disease-modifying treatment for Alzheimer's disease (AD). Recently, the role of microglia in disease, particularly AD, has gained great interest, following the identification of several disease risk-associated genes that are highly expressed in microglia. Microglia play a critical homeostatic role in the brain, with neuroinflammatory and phagocytic mechanisms being of particular importance. Here, we review the role of NLRP3, the complement system, and the triggering receptor expressed in myeloid cells 2 (TREM2) in modulating microglial functions. We have reviewed the targets, their molecular pathways and the therapeutic interventions aimed at modulating these targets, in the hope of discovering a novel therapeutic approach for the treatment of AD. LINKED ARTICLES: This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.

Publication types

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

MeSH terms

  • Alzheimer Disease / immunology*
  • Animals
  • Complement System Proteins / immunology
  • Humans
  • Inflammation / immunology
  • Membrane Glycoproteins / immunology
  • Microglia / immunology*
  • NLR Family, Pyrin Domain-Containing 3 Protein / immunology
  • Phagocytosis
  • Receptors, Immunologic / immunology

Substances

  • Membrane Glycoproteins
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Receptors, Immunologic
  • TREM2 protein, human
  • Complement System Proteins