Abstract
Amyloid beta (Aβ)-induced abnormal neuroinflammation is recognized as a major pathological feature of Alzheimer’s disease (AD), which results in memory impairment. Research exploring low-grade systemic inflammation and its impact on the development and progression of neurodegenerative disease has increased. A particular research focus has been whether systemic inflammation arises only as a secondary effect of disease, or it is also a cause of pathology. The inflammasomes, and more specifically the NLRP3 inflammasome, are crucial components of the innate immune system and are usually activated in response to infection or tissue damage. Although inflammasome activation plays critical roles against various pathogens in host defense, overactivation of inflammasome contributes to the pathogenesis of inflammatory diseases, including acute central nervous system (CNS) injuries and chronic neurodegenerative diseases, such as AD. This review summarizes the current literature on the role of the NLRP3 inflammasome in the pathogenesis of AD, and its involvement in infections, particularly SARS-CoV-2. NLRP3 might represent the crossroad between the hypothesized neurodegeneration and the primary COVID-19 infection.
Highlights
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Several studies showed that the NLRP3 inflammasome and IL-1β are implicated in the inflammatory response during lung injury and acute respiratory distress syndrome (ARDS) [76,77]
The NLRP3 inflammasome might represent the crossroad between SARS–CoV–2 infection and neurodegenerative outcomes depending on numerous factors, like the extension of the ground inflammatory response or the leukocytes invasion/migration to the brain [100]
Summary
Alzheimer’s disease (AD) is the most common neurodegenerative disease in older people representing the most frequent form of dementia worldwide [1]. Altered gene expression in the regulation of the immune system in AD and its contribution to the pathology, support a pathogenic role of CNS–resident myeloid cells, like microglia, in the evolution of the disease [34,35]. The secretion of proinflammatory cytokines IL-1β and IL-18 is mainly induced by microglia and astrocytes, and drives the inflammatory responses contributing to the neuronal damage and the phagocytic capacity of microglial cells [45,48]. Microglia express several PRRs, which detect modifications in the CNS environment through recognizing DAMPs and PAMPs and send converging signals to promote a spectrum of microglial responses from surveillance to activation [40]. Microglia assume different morphologies, and produce several cytotoxic molecules, including proinflammatory cytokines, inflammatory mediators like nitric oxide (NO), and reactive oxygen species (ROS) [49]. This review presents an overview of the findings in current research focusing on NLRP3 activation and the possible implication in AD
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