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Current Neuropharmacology

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Review Article

Alzheimer’s Disease: New Concepts on the Role of Autoimmunity and NLRP3 Inflammasome in the Pathogenesis of the Disease

Author(s): Cinzia Severini*, Christian Barbato, Maria Grazia Di Certo, Francesca Gabanella, Carla Petrella, Arianna Di Stadio, Marco de Vincentiis, Antonella Polimeni, Massimo Ralli and Antonio Greco

Volume 19, Issue 4, 2021

Published on: 21 June, 2020

Page: [498 - 512] Pages: 15

DOI: 10.2174/1570159X18666200621204546

Price: $65

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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. Increasing 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 macrophages into the brain, which in turn aggravate AD pathology.

The present review aims to update the current knowledge on the role of autoimmunity and neuroinflammation 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 inflammasome and the associated receptors could be a potential pharmacological strategy since its inhibition would selectively reduce AD neuroinflammation.

Keywords: Alzheimer's disease, autoimmunity, neuroinflammation, microglial NLRP3 inflammasome, microbiota-gutinflammasome- brain-axis, therapeutic targets.

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