Cited by 641Inflammasome and immune disordersNeuroinflammation and Neurodegeneration MechanismsImmune Response and Inflammation

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Inflammasomes in the CNS

Walsh, John G., Muruve, Daniel A., Power, Christopher·2014·Nature Reviews Neuroscience

DOI 10.1038/nrn3638

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Abstract

Microglia and macrophages in the CNS contain multimolecular complexes termed inflammasomes. Inflammasomes function as intracellular sensors for infectious agents as well as for host-derived danger signals that are associated with neurological diseases, including meningitis, stroke and Alzheimer's disease. Assembly of an inflammasome activates caspase 1 and, subsequently, the proteolysis and release of the cytokines interleukin-1β and interleukin-18, as well as pyroptotic cell death. Since the discovery of inflammasomes in 2002, there has been burgeoning recognition of their complexities and functions. Here, we review the current understanding of the functions of different inflammasomes in the CNS and their roles in neurological diseases.

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Influential
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Background
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Background
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Background
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Background
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Background
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Background
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BackgroundInfluential
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Background
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BackgroundInfluential
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Background
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Low Cellular NAD+ Compromises Lipopolysaccharide-Induced Inflammatory Responses via Inhibiting TLR4 Signal Transduction in Human Monocytes
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“Then, a second signal (signal 2), indicative of cellular damage such as extracellular ATP or crystals precipitated from urate or cholesterol (18), induces an assembly of the inflammasome, leading to an autolytical processing of procaspase-1 to active caspase-1.”
Background
Brainiac Caspases: Beyond the Wall of Apoptosis
Espinosa‐Oliva, A. M., García‐Revilla, J., Alonso-Bellido, I. M., & Burguillos, M. Á. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00500 · Cited by 36
Effects of α-lipoic acid on LPS-induced neuroinflammation and NLRP3 inflammasome activation through the regulation of BV-2 microglial cells activation
Kim, S. M., Ha, J. S., Han, A. R., Cho, S., & Yang, S.-J. (2019) · BMB Reports · doi:10.5483/bmbrep.2019.52.10.026 · Cited by 39
The “mitochondrial stress responses”: the “Dr. Jekyll and Mr. Hyde” of neuronal disorders
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“…by recognition of mtDAMPs from pattern recognition receptors that may be expressed by microglia, astrocytes, and macrophages (Lampron et al., 2013; Walsh et al., 2014; Freeman et al., 2017), but also by oligodendrocytes (McKenzie et al., 2018), neurons (Kaushal et al., 2015) and endothelial cells…”
Background
Brain xQTL map: Integrating the genetic architecture of the human brain transcriptome and epigenomePreprint
Ng, B., White, C. C., Klein, H., Sieberts, S., Aubin, C., Patrick, E., Xu, J., Yu, L., Gaiteri, C., Bennett, D. A. A., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/142927 · Cited by 39
Methylene Blue Inhibits Caspases by Oxidation of the Catalytic Cysteine
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“Firstly, transcription factors, it was found that nuclear factor erythroid 2-related factor 2 (Nrf2) activation reduced the expression levels of reactive oxygen species (ROS), nucleotide-binding oligomerization domain- (NOD-) like receptor family Pyrin domain 3 (NLRP3), and IL-1 β in BV2 microglia, and played a protec…”
BackgroundInfluential
The Ketone Body β-Hydroxybutyrate Does Not Inhibit Synuclein Mediated Inflammasome Activation in Microglia
Deora, V., Albornoz, E. A., Zhu, K., Woodruff, T. M., & Gordon, R. (2017) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-017-9754-5 · Cited by 36
Expression profile of pattern recognition receptors in skeletal muscle of SOD1 (G93A) amyotrophic lateral sclerosis (ALS) mice and sporadic ALS patients
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Oridonin relieves depressive‐like behaviors by inhibiting neuroinflammation and autophagy impairment in rats subjected to chronic unpredictable mild stress
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Disulfiram downregulates ferredoxin 1 to maintain copper homeostasis and inhibit inflammation in cerebral ischemia/reperfusion injury
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“The inflammasome protein complex has recently emerged as a pivotal component of the innate immune response during ischemic stroke 49 .”
Background
Looking for Pyroptosis‐Modulating miRNAs as a Therapeutic Target for Improving Myocardium Survival
Lee, S., Choi, E., Cha, M., & Hwang, K. (2015) · Mediators of Inflammation · doi:10.1155/2015/254871 · Cited by 37
Synthetic Oligodeoxynucleotides Containing Multiple Telemeric TTAGGG Motifs Suppress Inflammasome Activity in Macrophages Subjected to Oxygen and Glucose Deprivation and Reduce Ischemic Brain Injury in Stroke-Prone Spontaneously Hypertensive Rats
Zhao, J., Mou, Y., Bernstock, J. D., Klimanis, D., Wang, S., Spatz, M., Maric, D., Johnson, K. R., Klinman, D. M., Li, X., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0140772 · Cited by 37
“Critically all of these factors have been implicated in the activation of the NLRP3 inflammasome [58,59].”
Background
Early onset of inflammation during ontogeny of bipolar disorder: the NLRP2 inflammasome gene distinctly differentiates between patients and healthy controls in the transition between iPS cell and neural stem cell stages
Vizlin‐Hodzic, D., Zhai, Q., Illes, S., Södersten, K., Truvé, K., Parris, T. Z., Sobhan, P. K., Salmela, S., Kosalai, S. T., Kanduri, C., et al. (2017) · Translational Psychiatry · doi:10.1038/tp.2016.284 · Cited by 35
Transgenic Mice Overexpressing Serum Retinol-Binding Protein Develop Progressive Retinal Degeneration through a Retinoid-Independent Mechanism
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NLRP3 inflammasome activity and periodontal disease pathogenesis–A bidirectional relationship
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“Dysregulated inflammasome activity is a hallmark of many multi-factorial diseases with an inflammatory component, such as autoimmune disorders; cardiovascular diseases; bacterial, fungal, or viral infections; and cancer and neurological diseases (Man, 2018; Strowig et al., 2012; Walsh et al., 2014).”
Background
Repeated daily administration of increasing doses of lipopolysaccharide provides a model of sustained inflammation-induced depressive-like behaviour in mice that is independent of the NLRP3 inflammasome
Wickens, R. A., Donck, L. V., Mackenzie, A. B., & Bailey, S. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.07.041 · Cited by 40
“The innate immune sensor nucleotide-binding domain, the leucinerich repeat, and the pyrin domain containing protein (NLRP)3 inflammasome is a multi-protein complex that is responsible for the cleavage of proinflammatory cytokines, proIL-1β and proIL-18, in response to a range of pathogenic and endogenous danger signal…”
Background
Pro- and Anti-inflammatory Effects of High Cholesterol Diet on Aged Brain
Chen, Y., Yin, M., Cao, X., Hu, G., & Xiao, M. (2018) · Aging and Disease · doi:10.14336/ad.2017.0706 · Cited by 38
“The second signal is that mature caspase-1, ‘catalyzed’ by ASC, cleaves proIL-1β to mature IL-1 [31, 32].”
Background
HER2 Heterogeneity Is Associated with Poor Survival in HER2-Positive Breast Cancer
Hosonaga, M., Arima, Y., Sampetrean, O., Komura, D., Koya, I., Sasaki, T., Sato, E., Okano, H., Kudoh, J., Ishikawa, S., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082158 · Cited by 35
“The activation of inflammasomes has been reported to be associated with neurological diseases such as meningitis, stroke, and Alzheimer’s disease [13].”
Background
Simvastatin mitigates depressive-like behavior in ovariectomized rats: Possible role of NLRP3 inflammasome and estrogen receptors’ modulation
Menze, E. T., Ezzat, H., Shawky, S. A., Sami, M., Selim, E. H., Ahmed, S., Maged, N., Nadeem, N., Eldash, S., & Michel, H. E. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107582 · Cited by 35
Discovery of chalcone analogues as novel NLRP3 inflammasome inhibitors with potent anti-inflammation activities
Zhang, C., Hu, Y., Sun, P., Hua, L., Liang, S., Ou, Y., Wu, D., Wu, X., Chen, H. H., Hao, Y., et al. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113417 · Cited by 34
Targeting the gasdermin D as a strategy for ischemic stroke therapy
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Anti-neuroinflammatory effects of novel 5,6-dihydrobenzo[h]quinazolin-2-amine derivatives in lipopolysaccharide-stimulated BV2 microglial cells
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Impeding the combination of astrocytic ASCT2 and NLRP3 by talniflumate alleviates neuroinflammation in experimental models of Parkinson's disease
Liu, Y., Liu, T., Zhou, Y., Li, W., Wang, M., Song, N., Zhang, W., Jiang, J., Yuan, S., Ding, J., et al. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.07.021 · Cited by 36
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Multiple beneficial effects of melanocortin MC4 receptor agonists in experimental neurodegenerative disorders: Therapeutic perspectives
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“…neuronal circuits, synaptic plasticity and remodelling of discrete networks (Banerjee et al., 2010; Drouin-Ouellet and Cicchetti, 2012; Giuliani et al., 2010, 2012; Iqbal and Grundke-Iqbal, 2011; Lo, 2010; Moskowitz et al., 2010; Walsh et al., 2014; Zhang et al., 2011; Zipp and Aktas, 2006).”
Increased expression of ER stress, inflammasome activation, and mitochondrial biogenesis-related genes in peripheral blood mononuclear cells in major depressive disorder
Munshi, S., Alarbi, A. M., Zheng, H., Kuplicki, R., Burrows, K., Figueroa‐Hall, L. K., Victor, T. A., Aupperle, R. L., Khalsa, S. S., Paulus, M. P., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02695-2 · Cited by 37
The Role of Neuroinflammation in Neurodegenerative Disorders
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2-BFI Provides Neuroprotection Against Inflammation and Necroptosis in a Rat Model of Traumatic Brain Injury
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“Recently, the NLRP3 inflammasome, a core component of the innate immune system, has been highlighted to mediate the maturation and secretion of proinflammatory cytokines, especially IL-1β, and therefore play a critical role in the initiation and amplification of the inflammatory response (Walsh et al., 2014).”
Background
Intra-arterial Stem Cell Therapy Diminishes Inflammasome Activation After Ischemic Stroke: a Possible Role of Acid Sensing Ion Channel 1a
Vats, K., Sarmah, D., Datta, A., Saraf, J., Kaur, H., Pravalika, K., Wanve, M., Kalia, K., Borah, A., Dave, K. R., et al. (2019) · Journal of Molecular Neuroscience · doi:10.1007/s12031-019-01460-3 · Cited by 34
Concurrent suppression of Aβ aggregation and NLRP3 inflammasome activation for treating Alzheimer's disease
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The expressions of NLRP1, NLRP3, and AIM2 inflammasome complexes in the contusive spinal cord injury rat model and their responses to hormonal therapy
Majidpoor, J., Khezri, Z., Rostamzadeh, P., Mortezaee, K., Rezaie, M. J., Fathi, F., Abouzaripour, M., Bariki, M. G., Moradi, F., Shirazi, R., et al. (2020) · Cell and Tissue Research · doi:10.1007/s00441-020-03250-5 · Cited by 33
TSPO Ligands PK11195 and Midazolam Reduce NLRP3 Inflammasome Activation and Proinflammatory Cytokine Release in BV-2 Cells
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“Dysfunction of the neuroimmune or neuroendocrine system results in profound effects on the CNS through the neuroendocrine-immune network.”
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Inflammatory Mechanisms in Parkinson’s Disease: From Pathogenesis to Targeted Therapies
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“In the time course, microglia activation begins within 1–4 h, peaks in 1–3 days, declines at day 7, and returns to physiological level in 3–4 weeks after ICH (Zhou et al., 2014; Wan et al., 2016; Zhu et al., 2019).”
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Role of Na+/K+-ATPase in ischemic stroke: in-depth perspectives from physiology to pharmacology
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Inflammasomes as mediators of inflammation in HIV-1 infection
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“A wide range of stimuli in the cytosol have been found to initiate the activation of NLRP3, including potassium efflux, calcium accumulation, ATP, and cathepsin release through lysosomal damage or mitochondrial-injury-induced ROS production, to name but a few of the most investigated mechanisms [46,48].”
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Single-Cell Analysis for Glycogen Localization and Metabolism in Cultured Astrocytes
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Authors: Walsh, J. G., Muruve, D. A., & Power, C.
Affiliations: University of Alberta (CA)
University of Calgary (CA)
Corresponding author: Power, Christopher
ORCID: Muruve, Daniel A.
Power, Christopher
Venue: Nature Reviews Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2014-01-08
Volume: 15
Issue: 2
Pages: 84-97
ISSN: 1471-003X (ISSN-L)
1471-0048
DOI: 10.1038/nrn3638
OpenAlex: W1981649246
Cited by: 637
References: 149
Citations by year: 2026: 25 · 2025: 18 · 2024: 46 · 2023: 49 · 2022: 77 · 2021: 67 · 2020: 76 · 2019: 58 · 2018: 51 · 2017: 47 · 2016: 57 · 2015: 43 · 2014: 22
FWCI: 5.34
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Neuroscience (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: inflammasome, central nervous system, caspase-1, IL-1β, IL-18, pyroptosis, microglia, macrophages, neurological disorders, meningitis, stroke, Alzheimer's disease, innate immunity, damage-associated molecular patterns
MeSH terms: Animals, Central Nervous System, Humans, Macrophages, Nervous System Diseases, Neuroglia, Inflammasomes

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