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. In-creasing evidence suggests that self-misfolded proteins stimulate an immune response mediated by glial cells, inducing the release of inflammatory mediators and the recruitment of peripheral macro-phages into the brain, which in turn aggravate AD pathology. The present review aims to update the current knowledge on the role of autoimmunity and neuroin-flammation in the pathogenesis of the disease, indicating a 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 of the NLRP3 in-flammasome and the associated receptors could be a potential pharmacological strategy since its inhibition would selectively reduce AD neuroinflammation.
Alzheimer’s disease: New concepts on the role of autoimmunity and NLRP3 inflammasome in the pathogenesis of the disease
Ralli, Massimo;
2021-01-01
Abstract
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. In-creasing evidence suggests that self-misfolded proteins stimulate an immune response mediated by glial cells, inducing the release of inflammatory mediators and the recruitment of peripheral macro-phages into the brain, which in turn aggravate AD pathology. The present review aims to update the current knowledge on the role of autoimmunity and neuroin-flammation in the pathogenesis of the disease, indicating a 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 of the NLRP3 in-flammasome and the associated receptors could be a potential pharmacological strategy since its inhibition would selectively reduce AD neuroinflammation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
