The role of neuronal NLRP1 inflammasome in Alzheimer's disease: bringing neurons into the neuroinflammation game

Jeremy Kean Yi Yap, Benjamin Simon Pickard, Elaine Wan Ling Chan, Sook Yee Gan

Research output: Contribution to journalReview article

7 Citations (Scopus)
2 Downloads (Pure)

Abstract

The innate immune system and inflammatory response in the brain have critical impacts on the pathogenesis of many neurodegenerative diseases including Alzheimer’s disease (AD). In the central nervous system (CNS), the innate immune response is primarily mediated by microglia. However, non-glial cells such as neurons could also partake in inflammatory response independently through inflammasome signalling. The NLR family pyrin domain-containing 1 (NLRP1) inflammasome in the CNS is primarily expressed by pyramidal neurons and oligodendrocytes. NLRP1 is activated in response to amyloid-β (Aβ) aggregates, and its activation subsequently cleaves caspase-1 into its active subunits. The activated caspase-1 proteolytically processes interleukin-1β (IL-1β) and interleukin-18 (IL-18) into maturation whilst co-ordinately triggers caspase-6 which is responsible for apoptosis and axonal degeneration. In addition, caspase-1 activation induces pyroptosis, an inflammatory form of programmed cell death. Studies in murine AD models indicate that the Nlrp1 inflammasome is indeed upregulated in AD and neuronal death is observed leading to cognitive decline. However, the mechanism of NLRP1 inflammasome activation in AD is particularly elusive, given its structural and functional complexities. In this review, we examine the implications of the human NLRP1 inflammasome and its signalling pathways in driving neuroinflammation in AD.

Original languageEnglish
Pages (from-to)7741-7753
Number of pages13
JournalMolecular Neurobiology
Volume56
Issue number11
Early online date20 May 2019
DOIs
Publication statusPublished - 1 Nov 2019

Keywords

  • Alzheimer’s disease
  • caspase-1
  • interleukin-18
  • interleukin-1β
  • neuroinflammation
  • NLRP1 inflammasome

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