The role of inflammasomes in vascular cognitive impairment

Poh, Luting; Sim, Wei Liang; Jo, Dong-Gyu; Dinh, Quynh Nhu; Drummond, Grant; Sobey, Christopher; Chen, Christopher Li-Hsian; Lai, Mitchell KP; Fann, David Y; Arumugam, Thiruma

doi:10.26181/21060622.v1

1190262_Poh,L_2022.pdf (1.82 MB)

The role of inflammasomes in vascular cognitive impairment

journal contribution

posted on 2022-09-08, 05:06 authored by Luting Poh, Wei Liang Sim, Dong-Gyu Jo, Quynh Nhu DinhQuynh Nhu Dinh, Grant DrummondGrant Drummond, Christopher SobeyChristopher Sobey, Christopher Li-Hsian Chen, Mitchell KP Lai, David Y Fann, Thiruma ArumugamThiruma Arumugam

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.

Funding

This work was supported by the National Medical Research Council Research Grants (NMRC-CBRG-0102/2016; NMRC/CSA-SI/007/2016 and NMRC/OFIRG/0036/2017), Singapore.

History

Publication Date

2022-01-09

Journal

Molecular Neurodegeneration

Volume

17

Issue

1

Article Number

4

Pagination

28p.

Publisher

Springer Nature

ISSN

1750-1326

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