The role of inflammasomes in vascular cognitive impairment

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.