The role of inflammasomes in vascular cognitive impairment

Mol Neurodegener. 2022 Jan 9;17(1):4. doi: 10.1186/s13024-021-00506-8.

Abstract

There is an increasing prevalence of Vascular Cognitive Impairment (VCI) worldwide, and several studies have suggested that Chronic Cerebral Hypoperfusion (CCH) plays a critical role in disease onset and progression. However, there is a limited understanding of the underlying pathophysiology of VCI, especially in relation to CCH. Neuroinflammation is a significant contributor in the progression of VCI as increased systemic levels of the proinflammatory cytokine interleukin-1β (IL-1β) has been extensively reported in VCI patients. Recently it has been established that CCH can activate the inflammasome signaling pathways, involving NLRP3 and AIM2 inflammasomes that critically regulate IL-1β production. Given that neuroinflammation is an early event in VCI, it is important that we understand its molecular and cellular mechanisms to enable development of disease-modifying treatments to reduce the structural brain damage and cognitive deficits that are observed clinically in the elderly. Hence, this review aims to provide a comprehensive insight into the molecular and cellular mechanisms involved in the pathogenesis of CCH-induced inflammasome signaling in VCI.

Keywords: Chronic cerebral Hypoperfusion; Inflammasome; Inflammation; Vascular cognitive impairment; Vascular dementia.

Publication types

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

MeSH terms

  • Aged
  • Brain Injuries*
  • Brain Ischemia* / metabolism
  • Cognitive Dysfunction* / metabolism
  • Cytokines
  • Humans
  • Inflammasomes / metabolism
  • Interleukin-1beta / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism

Substances

  • Cytokines
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein