Is Alzheimer's disease an inflammasomopathy?

Ageing Res Rev. 2019 Dec:56:100966. doi: 10.1016/j.arr.2019.100966. Epub 2019 Sep 29.

Abstract

Alzheimer's disease (AD) is the most common form of dementia in the elderly and, despite the tremendous efforts researchers have put into AD research, there are no effective options for prevention and treatment of the disease. The best way to reach this goal is to clarify the mechanisms involved in the onset and progression of AD. In the last few years the views about the drivers of AD have been changing and nowadays it is believed that neuroinflammation takes center stage in disease pathogenesis. Herein, we provide an overview about the role of neuroinflammation in AD describing the role of microglia and astroglia is this process. Then, we will debate the NLRP3 inflammasome putting the focus on its activation through the canonical, non-canonical and alternative pathways and the triggers involved herein namely endoplasmic reticulum stress, mitochondrial dysfunction, reactive oxygen species and amyloid β peptide. Data supporting the hypothesis that inflammasome-mediated peripheral inflammation may contribute to AD pathology will be presented. Finally, a brief discussion about the therapeutic potential of NLRP3 inflammasome modulation is also provided.

Keywords: Beta-amyloid; ER stress; Mitochondria; NLRP3 inflammasome; Reactive oxygen species.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Humans
  • Inflammasomes / metabolism*
  • Inflammation
  • Microglia / metabolism*
  • Microglia / pathology
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Proteostasis Deficiencies / metabolism*
  • Proteostasis Deficiencies / pathology
  • Reactive Oxygen Species / metabolism

Substances

  • Amyloid beta-Protein Precursor
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Reactive Oxygen Species