NLRP3 inflammasome signalling in Alzheimer's disease

Neuropharmacology. 2024 Jul 1:252:109941. doi: 10.1016/j.neuropharm.2024.109941. Epub 2024 Mar 31.

Abstract

Every year, 10 million people develop dementia, the most common of which is Alzheimer's disease (AD). To date, there is no way to prevent cognitive decline and therapies are limited. This review provides a neuroimmunological perspective on the progression of AD, and discusses the immune-targeted therapies that are in preclinical and clinical trials that may impact the development of this disease. Specifically, we look to the role of the NLRP3 inflammasome, its triggers in the brain and how its activation can contribute to the progression of dementia. We summarise the range of inhibitors targeting the NLRP3 inflammasome and its downstream pathways that are under investigation, and discuss future therapeutic perspectives for this devastating condition.

Keywords: Alzheimer's disease; Immune-targeted therapies; Microglia; NLRP3 inflammasome; Neuroimmunology; Preclinical models.

Publication types

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

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / immunology
  • Alzheimer Disease* / metabolism
  • Animals
  • Brain / immunology
  • Brain / metabolism
  • Humans
  • Inflammasomes* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein* / antagonists & inhibitors
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Signal Transduction* / drug effects
  • Signal Transduction* / physiology

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human