Neuroinflammation in Alzheimer’s Disease: Focus on NLRP1 and NLRP3 Inflammasomes

Toscano, Eliana Cristina de Brito; Rocha, Natália Pessoa; Lopes, Beatriz Noele Azevedo; Suemoto, Cláudia Kimie; Teixeira, Antônio Lúcio

doi:10.2174/1389203722666210916141436

Cited by 15 publications

(8 citation statements)

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“…With the development of neurobiology, the role of neuroinflammation in nervous system disorders has been widely investigated. Studies have shown that neuroinflammation has a critical role in the pathogenesis of neurological disorders ( Jayaraj et al, 2019 ; Mukhara et al, 2020 ; de Brito Toscano et al, 2021 ). SIRT2, a type of NAD+ dependent deacetylases, is predominantly expressed in the cytoplasm of cells in the mammalian CNS ( Ma et al, 2020 ; Chen et al, 2021 ), which suggests that SIRT2 has a significant role in diseases with neuroinflammatory components ( Wang et al, 2016 , 2020 ; Figure 4 and Table 1 ).…”

Section: Sirtuin 2 and Neuroinflammatory Disordersmentioning

confidence: 99%

Will Sirtuin 2 Be a Promising Target for Neuroinflammatory Disorders?

Zhang

2022

Front. Cell. Neurosci.

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Neuroinflammatory disorder is a general term that is associated with the progressive loss of neuronal structure or function. At present, the widely studied diseases with neuroinflammatory components are mainly divided into neurodegenerative and neuropsychiatric diseases, namely, Alzheimer’s disease, Parkinson’s disease, depression, stroke, and so on. An appropriate neuroinflammatory response can promote brain homeostasis, while excessive neuroinflammation can inhibit neuronal regeneration and damage the central nervous system. Apart from the symptomatic treatment with cholinesterase inhibitors, antidepressants/anxiolytics, and neuroprotective drugs, the treatment of neuroinflammation is a promising therapeutic method. Sirtuins are a host of class III histone deacetylases, that require nicotinamide adenine dinucleotide for their lysine residue deacetylase activity. The role of sirtuin 2 (SIRT2), one of the sirtuins, in modulating senescence, myelin formation, autophagy, and inflammation has been widely studied. SIRT2 is associated with many neuroinflammatory disorders considering it has deacetylation properties, that regulate the entire immune homeostasis. The aim of this review was to summarize the latest progress in regulating the effects of SIRT2 on immune homeostasis in neuroinflammatory disorders. The overall structure and catalytic properties of SIRT2, the selective inhibitors of SIRT2, the relationship between immune homeostasis and SIRT2, and the multitasking role of SIRT2 in several diseases with neuroinflammatory components were discussed.

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Section: Sirtuin 2 and Neuroinflammatory Disordersmentioning

confidence: 99%

Will Sirtuin 2 Be a Promising Target for Neuroinflammatory Disorders?

Zhang

2022

Front. Cell. Neurosci.

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“…A recent study summarized the role of NLRP1 and NLRP3 in AD pathogenesis. However, the relationship between pyroptosis and AD induced by NLRC4, AIM2 and Pyrin needs to be further elucidated ( de Brito Toscano et al, 2021 ). Tau tangle and Aβ plaque are widely recognized as major pathogenic pathogens in AD, and tau and Aβ protein-induced pyroptosis and neuroinflammation are closely associated with AD-related brain damage ( Tiwari et al, 2019 ).…”

Section: Research Progress In Relationship Between Pyroptosis and Alz...mentioning

confidence: 99%

Pyroptosis as a candidate therapeutic target for Alzheimer’s disease

Huang

Li²,

Luo³

et al. 2022

Front. Aging Neurosci.

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Pyroptosis is a form of cell death mediated by inflammasomes and gasdermins, and the relevance of pyroptosis to neurodegenerative diseases is currently receiving increasing attention. Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease that is closely associated with neuroinflammation. Its main pathological features include β-amyloid (Aβ) deposition, Tau protein hyperphosphorylation and neuronal loss. Aβ, tau-induced microglia pyroptosis and polarization leading to neuroinflammation play an important role in the pathogenesis of AD. Studying the pathogenesis and treatment of AD based on cellular pyroptosis has become a new direction in AD research. In this paper, we review the research progress of pyroptosis and will focus on the pathogenic roles of pyroptosis in AD and the role of targeted inhibition of inflammasome-dependent pyroptosis in AD treatment. These results deepen our understanding of the pathogenesis of AD and provide ideas for the development of new drugs based on the regulation of pyroptosis in AD patients.

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“… 11 , 12 Recently, more studies suggested that pyroptosis plays a role in the pathogenesis of neurocognitive diseases, including Alzheimer’s and Parkinson’s disease. 13 , 14 It was chiefly reported that silencing pyroptosis-associated inflammasome could attenuate surgery-induced cognitive impairments. 15–17 Subsequently, the attenuated decline in learning and memory following the inhibition of caspase-1-associated pyroptotic inflammation after surgery was investigated.…”

Section: Introductionmentioning

confidence: 99%

VRT-043198 Ameliorates Surgery-Induced Neurocognitive Disorders by Restoring the NGF and BNDF Expression in Aged Mice

Qi¹,

Guo²,

Li³

et al. 2022

NDT

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Background Perioperative neurocognitive disorders (PND) are common surgical complications in the elderly. Pyroptosis-associated inflammation has been suggested to participate in a series of neurocognitive diseases, including Alzheimer’s disease. Given that VRT-043198 can reportedly inhibit caspase-1-induced pyroptosis, this study sought to determine whether VRT-043198 reduced PND in a mouse model following abdominal exploratory laparotomy. Methods 20-month-old male C57/BL mice were used to establish an abdominal exploratory laparotomy (AEL) model of PND. VRT-043198 (1, 10 and 100 mg/kg) was administered intraperitoneally immediately after surgery. Thirty days post-surgery, the mice were evaluated in the Morris water maze test. Their number of neurons, neurotrophin nerve growth factor (NGF) levels and brain-derived neurotrophic factor (BDNF) were measured. In the hippocampus, A1-type astrocytes and M1-type microglia were assessed using an immunofluorescence assay and Western blot, respectively. Caspase-1 activity, IL-1β, IL-18, and PPAR-γ were also measured 24h after surgery. Results VRT-043198 administration increased the time to cross the platform and increased the ratio of distance and time in the targeted quadrant after surgery. Furthermore, it was found that VRT-043198 restored neuronal amount, increased NGF and BDNF and decreased the number of A1-type astrocytes and M1-type microglia. VRT-043198 also attenuated caspase-1 activity, downregulated IL-1β and IL-18, but increased PPAR-γ 24h post-surgery. Conclusion VRT-043198 improved PND in aged mice after abdominal exploratory laparotomy by restoring the NGF and BNDF expression. These results indicate that VRT-043198 may be a potential therapy for PND.

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Neuroinflammation in Alzheimer’s Disease: Focus on NLRP1 and NLRP3 Inflammasomes

Cited by 15 publications

References 0 publications

Will Sirtuin 2 Be a Promising Target for Neuroinflammatory Disorders?

Will Sirtuin 2 Be a Promising Target for Neuroinflammatory Disorders?

Pyroptosis as a candidate therapeutic target for Alzheimer’s disease

VRT-043198 Ameliorates Surgery-Induced Neurocognitive Disorders by Restoring the NGF and BNDF Expression in Aged Mice

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