The NLRP3 Inflammasome in the Pathogenesis and Treatment of Alzheimer's Disease

J Alzheimers Dis. 2021;84(2):579-598. doi: 10.3233/JAD-210660.

Abstract

Alzheimer's disease (AD) is the most common form of dementia. Although AD is one of the most socioeconomically devastating diseases confronting humanity, no "curative" disease modifying drug has been identified. Recent decades have witnessed repeated failures of drug trials and have called into question the utility of the amyloid hypothesis approach to AD therapeutics design. Accordingly, new neurochemical processes are being evaluated and explored as sources of alternative druggable targets. Among these newly identified targets, neuroinflammation is emerging as a front-runner, and within the realm of neuroinflammation, the inflammasome, particularly the NLRP3 complex, is garnering focussed attention. This review summarizes current data and approaches to understanding the role of the NLRP3 inflammasome in neuroinflammation and AD, and systematically identifies and evaluates multiple targets within the NLRP3 inflammasome cascade as putative drug targets.

Keywords: Alzheimer’s disease; NLRP3; dementia; inflammasome; innate immune.

Publication types

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

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / pathology
  • Humans
  • Inflammasomes*
  • NLR Family, Pyrin Domain-Containing 3 Protein*

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein