The NLRP3 inflammasome as a bridge between neuro-inflammation in metabolic and neurodegenerative diseases

Söderbom, Grażyna; Zeng, Bai-Yun

doi:10.1016/bs.irn.2020.03.023

Cited by 20 publications

(13 citation statements)

References 273 publications

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“…Although the precise pathogenesis of PD remains elusive, accumulating evidence indicates that inflammasome-induced neuroinflammation is an important component of PD etiopathogenesis. 29 , 30 In particular, the NLRP3 inflammasome, including NLRP3, ASC, and caspase 1, is the most studied inflammasome in PD. 9 To activate the NLRP3 inflammasome successfully, two signals have been proposed: (1) Signal 1 (priming).…”

Section: Discussionmentioning

confidence: 99%

Melatonin Attenuates Neuroinflammation by Down-Regulating NLRP3 Inflammasome via a SIRT1-Dependent Pathway in MPTP-Induced Models of Parkinson’s Disease

Zheng

Ruan

Yan

et al. 2021

JIR

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Background: Inflammasome-induced neuroinflammation is a key contributor to the pathology of Parkinson's disease (PD). NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation has been implicated in PD in postmortem human PD brains, indicating it as a potential target for PD treatment. Melatonin, a multitasking molecule, has been found to have anti-inflammatory activities, mediated by silence information regulator 1 (SIRT1). However, whether and how melatonin is involved in inflammasome-induced neuroinflammation in PD pathogenesis remains unclear. Methods: We investigated the potential anti-inflammatory effects of melatonin in vitro and in vivo, using 1-methyl-4-phenylpyridinium (MPP + )-simulated BV2 and primary microglia cell models, and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced murine PD model, with or without melatonin treatment. Rotarod, grip strength, and open-field tests were performed to measure the effects of melatonin on MPTP-induced motor disorders. Degeneration of dopaminergic neurons was evaluated by immunofluorescence. Changes in microglia were examined by immunofluorescence and Western blotting, and the expression levels of the involved signaling molecules were assessed by Western blotting and enzymelinked immunosorbent assay (ELISA). Intracellular reactive oxygen species (ROS) was detected using fluorescent probes via flow cytometry. Results: We found that melatonin significantly alleviated motor dysfunction and prevented MPTP-induced neurotoxicity in dopaminergic neurons. Additionally, melatonin reduced MPTP-induced microglial activation and suppressed NLRP3 inflammasome activity, and also inhibited IL-1β secretion. Moreover, in MPP + -primed BV2 cells, melatonin markedly restored the downregulation of SIRT1 and attenuated the activation of the NLRP3 inflammasome. This was reversed by SIRT1 inhibitor treatment. Conclusion:In conclusion, our data demonstrated that melatonin attenuates neuroinflammation by negatively regulating NLRP3 inflammasome activation via a SIRT1-dependent pathway in MPTP-induced PD models. These findings provide novel insights into the mechanism underlying the anti-inflammatory effects of melatonin in PD.

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Section: Discussionmentioning

confidence: 99%

Melatonin Attenuates Neuroinflammation by Down-Regulating NLRP3 Inflammasome via a SIRT1-Dependent Pathway in MPTP-Induced Models of Parkinson’s Disease

Zheng

Ruan

Yan

et al. 2021

JIR

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“…Lee et al also reported upregulation of NLRP3 and its downstream molecules in T2DM and atherosclerosis (35). Söderbom G et al identified the NLRP3 inflammasome as a bridge between neuro-inflammation in metabolic and neurodegenerative diseases (36). Thus, activation of NLRP3 appears to be a major mechanism in T2DMand its complications.…”

Section: Dm and Nlrp3mentioning

confidence: 97%

Diabetes Mellitus Promotes the Development of Atherosclerosis: The Role of NLRP3

Wang

et al. 2022

Front. Immunol.

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Atherosclerosis is one of the main complications of diabetes mellitus, involving a variety of pathogenic factors. Endothelial dysfunction, inflammation, and oxidative stress are hallmarks of diabetes mellitus and atherosclerosis. Although the ability of diabetes to promote atherosclerosis has been demonstrated, a deeper understanding of the underlying biological mechanisms is critical to identifying new targets. NLRP3 plays an important role in both diabetes and atherosclerosis. While the diversity of its activation modes is one of the underlying causes of complex effects in the progression of diabetes and atherosclerosis, it also provides many new insights for targeted interventions in metabolic diseases.

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“…These diseases are characterized by pathological changes in specific disease areas of the brain and degeneration of different neuronal subgroups (Dugger & Dickson, 2017). Despite the differences in clinical manifestations and neuronal vulnerability, the pathological processes appear similar, including antioxidant effects, anti‐inflammatory effects, anti‐apoptosis effects, improving the pathological features related to degenerative diseases, synaptic protection, and up‐regulation of nerve cells (Radi, Formichi, Battisti, & Federico, 2014; Söderbom & Zeng, 2020).…”

Section: Pharmacological Actionsmentioning

confidence: 99%

Ginsenosides in central nervous system diseases: Pharmacological actions, mechanisms, and therapeutics

Xian

et al. 2022

Phytotherapy Research

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The nervous system is one of the most complex physiological systems, and central nervous system diseases (CNSDs) are serious diseases that affect human health. Ginseng (Panax L.), the root of Panax species, are famous Chinese herbs that have been used for various diseases in China, Japan, and Korea since ancient times, and remain a popular natural medicine used worldwide in modern times. Ginsenosides are the main active components of ginseng, and increasing evidence has demonstrated that ginsenosides can prevent CNSDs, including neurodegenerative diseases, memory and cognitive impairment, cerebral ischemia injury, depression, brain glioma, multiple sclerosis, which has been confirmed in numerous studies. Therefore, this review summarizes the potential pathways by which ginsenosides affect the pathogenesis of CNSDs mainly including antioxidant effects, anti-inflammatory effects, anti-apoptotic effects, and nerve protection, which provides novel ideas for the treatment of CNSDs.

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The NLRP3 inflammasome as a bridge between neuro-inflammation in metabolic and neurodegenerative diseases

Cited by 20 publications

References 273 publications

Melatonin Attenuates Neuroinflammation by Down-Regulating NLRP3 Inflammasome via a SIRT1-Dependent Pathway in MPTP-Induced Models of Parkinson’s Disease

Melatonin Attenuates Neuroinflammation by Down-Regulating NLRP3 Inflammasome via a SIRT1-Dependent Pathway in MPTP-Induced Models of Parkinson’s Disease

Diabetes Mellitus Promotes the Development of Atherosclerosis: The Role of NLRP3

Ginsenosides in central nervous system diseases: Pharmacological actions, mechanisms, and therapeutics

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