NLRP3 Inflammasome: A Starring Role in Amyloid-β- and Tau-Driven Pathological Events in Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2021, Volume and Issue: 83(3), P. 939 - 961

Published: Aug. 6, 2021

Alzheimer’s disease (AD) is the most prevalent neurodegenerative commonly diagnosed among elderly population. AD characterized by loss of synaptic connections, neuronal death, and progressive cognitive impairment, attributed to extracellular accumulation senile plaques, composed insoluble aggregates amyloid-β (Aβ) peptides, intraneuronal formation neurofibrillary tangles shaped hyperphosphorylated filaments microtubule-associated protein tau. However, evidence showed that chronic inflammatory responses, with long-lasting exacerbated release proinflammatory cytokines reactive glial cells, contribute pathophysiology disease. NLRP3 inflammasome (NLRP3), a cytosolic multiprotein complex sensor wide range stimuli, was implicated in multiple neurological diseases, including AD. Herein, we review recent findings regarding involvement pathogenesis We address mechanisms priming activation cells Aβ species potential role vesicles progression. Neuronal death NLRP3-mediated pyroptosis, driven interneuronal tau propagation, also discussed. present considerable claim inhibition, undoubtfully therapeutic strategy for

Language: Английский

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Microglia in Alzheimer’s Disease: A Target for Therapeutic Intervention

Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Nov. 24, 2021

Alzheimer’s disease (AD) is one of the most common types age-related dementia worldwide. In addition to extracellular amyloid plaques and intracellular neurofibrillary tangles, dysregulated microglia also play deleterious roles in AD pathogenesis. Numerous studies have demonstrated that unbridled microglial activity induces a chronic neuroinflammatory environment, promotes β-amyloid accumulation tau pathology, impairs microglia-associated mitophagy. Thus, targeting may pave way for new therapeutic interventions. This review provides thorough overview pathophysiological role illustrates potential avenues microglia-targeted therapies, including modification, immunoreceptors, anti-inflammatory drugs.

Language: Английский

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Tau Pathology Drives Dementia Risk-Associated Gene Networks toward Chronic Inflammatory States and Immunosuppression

Cell Reports, Journal Year: 2020, Volume and Issue: 33(7), P. 108398 - 108398

Published: Nov. 1, 2020

To understand how neural-immune-associated genes and pathways contribute to neurodegenerative disease pathophysiology, we performed a systematic functional genomic analysis in purified microglia bulk tissue from mouse human AD, FTD, PSP. We uncover complex temporal trajectory of microglial-immune involving the type 1 interferon response associated with tau pathology early stages, followed by later signatures partial immune suppression and, subsequently, 2 response. find that genetic risk for dementias shows disease-specific patterns pathway enrichment. identify drivers two gene co-expression modules conserved human, representing competing arms activation (NAct) (NSupp) neurodegeneration. validate our findings using chemogenetics, experimental perturbation data, single-cell sequencing post-mortem brains. Our results refine understanding stage- microglial responses, implicate viral defense dementia highlight therapeutic windows.

Language: Английский

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Activation of NLRP3 Inflammasome and Onset of Alzheimer’s Disease

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: July 26, 2021

The nucleotide-binding domain leucine-rich repeat and pyrin containing receptor protein 3 (NLRP3) is an important pattern recognition in human innate immunity. Activation of the NLRP3 inflammasome play a key role pathogenesis Alzheimer’s disease (AD). Theories explaining activation include reactive oxygen species theory, lysosomal damage theory mitochondrial DNA theory. promotes occurrence AD by producing IL-1β, IL-18 other cytokines, then affecting deposition Aβ tau proteins. Over-activated often impair cell function induces immune-related diseases. Some mechanisms have been found to negatively regulate inflammasome, which may be through binding blocking mechanism, autophagy related abnormal cytokine secretion or interference gene expression regulation mechanism. In this review, we summarize possible inflammasomes affects AD, recent advances prevention treatment controlling inflammasomes. By researching inactivation it reveal from new perspective provide idea for AD.

Language: Английский

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NLRP3 inflammasome in neurodegenerative disease

Translational research, Journal Year: 2022, Volume and Issue: 252, P. 21 - 33

Published: Aug. 9, 2022

Language: Английский

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