Ricerc@Sapienza

Alzheimer's disease (AD), recognized as the most common neurodegenerative disorder, is clinically characterized by the presence of extracellular beta amyloid (Aβ) plaques and by intracellular neurofibrillary tau tangles, accompanied by glial activation and neuroinflammation. Increasing evidence suggests that self-misfolded proteins stimulate an immune response mediated by glial cells, inducing release of inflammatory mediators and the recruitment of peripheral macrophages into the brain, which in turn aggravate AD pathology. Aim of the present review is to update the current knowledge on the role of autoimmunity and neuroinflammation in the pathogenesis of the disease, indicating new target for therapeutic intervention. We mainly focused on the NLRP3 microglial inflammasome as a critical factor in stimulating innate immune responses, thus sustaining chronic inflammation. Additionally, we discussed the involvement of the NLRP3 inflammasome in the gut-brain axis. Direct targeting the NLRP3 inflammasome and the associated receptors could be a potential pharmacological strategy, since its inhibition would selectively reduce AD neuroinflammation.