Inflammasomes link vascular disease with neuroinflammation and brain disorders

Abstract

The role of inflammation in neurological disorders is increasingly recognised. Inflammatory processes are associated with the aetiology and clinical progression of migraine, psychiatric conditions, epilepsy, cerebrovascular diseases, dementia and neurodegeneration, such as seen in Alzheimer's or Parkinson's disease. Both central and systemic inflammatory actions have been linked with the development of brain diseases, suggesting that complex neuro-immune interactions could contribute to pathological changes in the brain across multiple temporal and spatial scales. However, the mechanisms through which inflammation impacts on neurological disease are improperly defined. To develop effective therapeutic approaches, it is imperative to understand how detrimental inflammatory processes could be blocked selectively, or controlled for prolonged periods, without compromising essential immune defence mechanisms. Increasing evidence indicates that common risk factors for brain disorders, such as atherosclerosis, diabetes, hypertension, obesity or infection involve the activation of NLRP3, NLRP1, NLRC4 or AIM2 inflammasomes, which are also associated with various neurological diseases. This review focuses on the mechanisms whereby inflammasomes, which integrate diverse inflammatory signals in response to pathogen-driven stimuli, tissue injury or metabolic alterations in multiple cell types and different organs of the body, could functionally link vascular- and neurological diseases and hence represent a promising therapeutic target.

Keywords: Inflammation; brain disease; inflammasome; neurodegeneration; systemic.

© The Author(s) 2016.

Figures

Figure 1.

Inflammasome signalling in different cell types involved in brain inflammation and injury. Because of the extensive literature data available, inflammasome signalling in monocytes and macrophages is not discussed in detail only pathways confirmed in the case of microglia. See detailed explanation in the text. Please note that triggers, pathways and downstream events of inflammasome activation were depicted in the figure only if experimental evidence is available for the given cell type.