Inflammaging and neurodegenerative diseases: Role of NLRP3 inflammasome activation in brain atherosclerotic vascular disease.

Abstract The activation of the NLRP3 inflammasome-IL-1β pathway has been clearly shown to be involved in the pathophysiology of cardiovascular diseases, but its role in cerebral atherosclerotic vascular disease has not been fully clarified. Here we provide an overview on the current knowledge about the relevance of the activation of this mechanism in the onset of acute brain atherosclerotic vascular disease and the subsequent tissue damage. Some variants of NLRP3-related genes seem to reduce the susceptibility to acute ischaemic stroke in selected cohorts, although no clear evidence exists either supporting or excluding any role of this pathway in its pathophysiology. Interestingly, robust experimental and clinical data support a major role of the activation of the NLRP3 inflammasome-IL-1β pathway in the post-event inflammatory cascade which leads to neurodegeneration. This evidence highlights a potential dual role of these molecules in brain pre- and post-ischaemic events, supporting the need for further studies, including clinical trials evaluating the modulation of this pathway for stroke prevention and post-stroke treatment.