Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C. & Gage, F. H. Mechanisms underlying inflammation in neurodegeneration. Cell140, 918–934 (2010). ArticleCASPubMedPubMed Central Google Scholar
Allan, S. M. & Rothwell, N. J. Cytokines and acute neurodegeneration. Nature Rev. Neurosci.2, 734–744 (2001). ArticleCAS Google Scholar
Martinon, F., Burns, K. & Tschopp, J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol. Cell10, 417–426 (2002). This article coined the term 'inflammasome' and described the complex for the first time. ArticleCASPubMed Google Scholar
Rathinam, V. A., Vanaja, S. K. & Fitzgerald, K. A. Regulation of inflammasome signaling. Nature Immunol.13, 333–342 (2012). ArticleCAS Google Scholar
Agostini, L. et al. NALP3 forms an IL-1β-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity20, 319–325 (2004). ArticleCASPubMed Google Scholar
Minkiewicz, J., de Rivero Vaccari, J. P. & Keane, R. W. Human astrocytes express a novel NLRP2 inflammasome. Glia61, 1113–1121 (2013). ArticlePubMed Google Scholar
Fernandes-Alnemri, T., Yu, J. W., Datta, P., Wu, J. & Alnemri, E. S. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature458, 509–513 (2009). ArticleCASPubMedPubMed Central Google Scholar
Faustin, B. et al. Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Mol. Cell25, 713–724 (2007). ArticleCASPubMed Google Scholar
Case, C. L. & Roy, C. R. Asc modulates the function of NLRC4 in response to infection of macrophages by Legionella pneumophila. mBio2, e00117-11 (2011). ArticleCASPubMedPubMed Central Google Scholar
Franchi, L., Munoz-Planillo, R. & Nunez, G. Sensing and reacting to microbes through the inflammasomes. Nature Immunol.13, 325–332 (2012). ArticleCAS Google Scholar
Allan, S. M., Tyrrell, P. J. & Rothwell, N. J. Interleukin-1 and neuronal injury. Nature Rev. Immunol.5, 629–640 (2005). ArticleCAS Google Scholar
John, G. R., Lee, S. C., Song, X., Rivieccio, M. & Brosnan, C. F. IL-1-regulated responses in astrocytes: relevance to injury and recovery. Glia49, 161–176 (2005). ArticlePubMed Google Scholar
Bergsbaken, T., Fink, S. L. & Cookson, B. T. Pyroptosis: host cell death and inflammation. Nature Rev. Microbiol.7, 99–109 (2009). ArticleCAS Google Scholar
Zhang, W. H. et al. Fundamental role of the Rip2/caspase-1 pathway in hypoxia and ischemia-induced neuronal cell death. Proc. Natl Acad. Sci. USA100, 16012–16017 (2003). This study provides strong evidence for a caspase 1-dependent cell death pathway that is localized in neurons, using caspase 1-knockout mice. ArticleCASPubMedPubMed Central Google Scholar
de Rivero Vaccari, J. P., Lotocki, G., Marcillo, A. E., Dietrich, W. D. & Keane, R. W. A molecular platform in neurons regulates inflammation after spinal cord injury. J. Neurosci.28, 3404–3414 (2008). ArticleCASPubMedPubMed Central Google Scholar
de Rivero Vaccari, J. P. et al. Therapeutic neutralization of the NLRP1 inflammasome reduces the innate immune response and improves histopathology after traumatic brain injury. J. Cereb. Blood Flow Metab.29, 1251–1261 (2009). One of several related studies to propose a novel role for NLRP1 activation in the response to acute brain injury. ArticleCASPubMed Google Scholar
Silverman, W. R. et al. The pannexin 1 channel activates the inflammasome in neurons and astrocytes. J. Biol. Chem.284, 18143–18151 (2009). ArticleCASPubMedPubMed Central Google Scholar
Wu, J., Fernandes-Alnemri, T. & Alnemri, E. S. Involvement of the AIM2, NLRC4, and NLRP3 inflammasomes in caspase-1 activation by Listeria monocytogenes. J. Clin. Immunol.30, 693–702 (2010). ArticleCASPubMedPubMed Central Google Scholar
Jamilloux, Y. et al. Inflammasome activation restricts Legionella pneumophila replication in primary microglial cells through flagellin detection. Glia61, 539–549 (2013). ArticlePubMed Google Scholar
Miao, E. A. et al. Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf. Nature Immunol.7, 569–575 (2006). ArticleCAS Google Scholar
Miao, E. A. et al. Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. Proc. Natl Acad. Sci. USA107, 3076–3080 (2010). ArticlePubMedPubMed Central Google Scholar
Kofoed, E. M. & Vance, R. E. Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity. Nature477, 592–595 (2011). ArticleCASPubMedPubMed Central Google Scholar
Zhao, Y. et al. The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus. Nature477, 596–600 (2011). ArticleCASPubMed Google Scholar
Vinzing, M. et al. NAIP and Ipaf control Legionella pneumophila replication in human cells. J. Immunol.180, 6808–6815 (2008). ArticleCASPubMed Google Scholar
Maier, J. K. et al. The neuronal apoptosis inhibitory protein is a direct inhibitor of caspases 3 and 7. J. Neurosci.22, 2035–2043 (2002). ArticleCASPubMedPubMed Central Google Scholar
Boyden, E. D. & Dietrich, W. F. Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nature Genet.38, 240–244 (2006). ArticleCASPubMed Google Scholar
Moayeri, M., Sastalla, I. & Leppla, S. H. Anthrax and the inflammasome. Microbes Infect.14, 392–400 (2012). ArticleCASPubMed Google Scholar
Finger, J. N. et al. Autolytic proteolysis within the function to find domain (FIIND) is required for NLRP1 inflammasome activity. J. Biol. Chem.287, 25030–25037 (2012). ArticleCASPubMedPubMed Central Google Scholar
Ebrahimi, C. M., Sheen, T. R., Renken, C. W., Gottlieb, R. A. & Doran, K. S. Contribution of lethal toxin and edema toxin to the pathogenesis of anthrax meningitis. Infect. Immun.79, 2510–2518 (2011). ArticleCASPubMedPubMed Central Google Scholar
Fink, S. L., Bergsbaken, T. & Cookson, B. T. Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms. Proc. Natl Acad. Sci. USA105, 4312–4317 (2008). ArticlePubMedPubMed Central Google Scholar
Levinsohn, J. L. et al. Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome. PLoS Pathog.8, e1002638 (2012). ArticlePubMedPubMed Central Google Scholar
D'Osualdo, A. et al. CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain. PLoS ONE6, e27396 (2011).
Geldhoff, M. et al. Genetic variation in inflammasome genes is associated with outcome in bacterial meningitis. Immunogenetics65, 9–16 (2013). ArticleCASPubMed Google Scholar
Bruey, J. M. et al. Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1. Cell129, 45–56 (2007). ArticleCASPubMed Google Scholar
Deveraux, Q. L. et al. Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases. EMBO J.18, 5242–5251 (1999). ArticleCASPubMedPubMed Central Google Scholar
Labbe, K., McIntire, C. R., Doiron, K., Leblanc, P. M. & Saleh, M. Cellular inhibitors of apoptosis proteins cIAP1 and cIAP2 are required for efficient caspase-1 activation by the inflammasome. Immunity35, 897–907 (2011). ArticleCASPubMed Google Scholar
Vince, J. E. et al. Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation. Immunity36, 215–227 (2012). ArticleCASPubMed Google Scholar
Pelegrin, P. & Surprenant, A. Pannexin-1 mediates large pore formation and interleukin-1β release by the ATP-gated P2X7 receptor. EMBO J.25, 5071–5082 (2006). ArticleCASPubMedPubMed Central Google Scholar
Karatas, H. et al. Spreading depression triggers headache by activating neuronal Panx1 channels. Science339, 1092–1095 (2013). ArticleCASPubMed Google Scholar
Qu, Y. et al. Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation. J. Immunol.186, 6553–6561 (2011). ArticleCASPubMed Google Scholar
Bargiotas, P., Krenz, A., Monyer, H. & Schwaninger, M. Functional outcome of pannexin-deficient mice after cerebral ischemia. Channels (Austin)6, 453–456 (2012). ArticleCAS Google Scholar
MacVicar, B. A. & Thompson, R. J. Non-junction functions of pannexin-1 channels. Trends Neurosci.33, 93–102 (2010). ArticleCASPubMed Google Scholar
Pontillo, A., Catamo, E., Arosio, B., Mari, D. & Crovella, S. NALP1/NLRP1 genetic variants are associated with Alzheimer disease. Alzheimer Dis. Assoc. Disord.26, 277–281 (2012). ArticleCASPubMed Google Scholar
Duncan, J. A. et al. Neisseria gonorrhoeae activates the proteinase cathepsin B to mediate the signaling activities of the NLRP3 and ASC-containing inflammasome. J. Immunol.182, 6460–6469 (2009). ArticleCASPubMed Google Scholar
Ichinohe, T., Lee, H. K., Ogura, Y., Flavell, R. & Iwasaki, A. Inflammasome recognition of influenza virus is essential for adaptive immune responses. J. Exp. Med.206, 79–87 (2009). ArticleCASPubMedPubMed Central Google Scholar
Mariathasan, S. et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature440, 228–232 (2006). ArticleCASPubMed Google Scholar
Halle, A. et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-β. Nature Immunol.9, 857–865 (2008). The first study to implicate inflammasome activation in response to a misfolded protein — in this case, amyloid-β. ArticleCAS Google Scholar
Martinon, F., Petrilli, V., Mayor, A., Tardivel, A. & Tschopp, J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature440, 237–241 (2006). ArticleCASPubMed Google Scholar
Hornung, V. et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nature Immunol.9, 847–856 (2008). ArticleCAS Google Scholar
Bauernfeind, F. G. et al. Cutting edge: NF-κB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J. Immunol.183, 787–791 (2009). ArticleCASPubMed Google Scholar
Ferrari, D. et al. Extracellular ATP triggers IL-1 beta release by activating the purinergic P2Z receptor of human macrophages. J. Immunol.159, 1451–1458 (1997). CASPubMed Google Scholar
Piccini, A. et al. ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1β and IL-18 secretion in an autocrine way. Proc. Natl Acad. Sci. USA105, 8067–8072 (2008). ArticlePubMedPubMed Central Google Scholar
Petrilli, V. et al. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ.14, 1583–1589 (2007). ArticleCASPubMed Google Scholar
Munoz-Planillo, R. et al. K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity38, 1142–1153 (2013). This study reports that all activators of the NLRP3 inflammasome mediate their actions through the triggering of a K+ efflux. ArticleCASPubMedPubMed Central Google Scholar
Schorn, C. et al. Sodium overload and water influx activate the NALP3 inflammasome. J. Biol. Chem.286, 35–41 (2011). ArticleCASPubMed Google Scholar
Compan, V. et al. Cell volume regulation modulates NLRP3 inflammasome activation. Immunity37, 487–500 (2012). A recent study that proposes cell volume changes as a conserved mechanism for regulating NLRP3 inflammasome activation, including within neurons. ArticleCASPubMed Google Scholar
Chu, J. et al. Cholesterol-dependent cytolysins induce rapid release of mature IL-1β from murine macrophages in a NLRP3 inflammasome and cathepsin B-dependent manner. J. Leukoc. Biol.86, 1227–1238 (2009). ArticleCASPubMedPubMed Central Google Scholar
Zaiss, A. K. et al. Antiviral antibodies target adenovirus to phagolysosomes and amplify the innate immune response. J. Immunol.182, 7058–7068 (2009). ArticleCASPubMed Google Scholar
Hoegen, T. et al. The NLRP3 inflammasome contributes to brain injury in pneumococcal meningitis and is activated through ATP-dependent lysosomal cathepsin B release. J. Immunol.187, 5440–5451 (2011). This study shows that NLPR3 activation promotes brain injury in pneumococcal meningitis. This contrasts with pneumococcal pneumonia, in which NLRP3 inflammasome activation is protective. ArticleCASPubMed Google Scholar
Codolo, G. et al. Triggering of inflammasome by aggregated α-synuclein, an inflammatory response in synucleinopathies. PLoS ONE8, e55375 (2013). ArticleCASPubMedPubMed Central Google Scholar
Cruz, C. M. et al. ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages. J. Biol. Chem.282, 2871–2879 (2007). ArticleCASPubMed Google Scholar
Zhou, R., Tardivel, A., Thorens, B., Choi, I. & Tschopp, J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nature Immunol.11, 136–140 (2010). ArticleCAS Google Scholar
Kaushik, D. K., Gupta, M., Kumawat, K. L. & Basu, A. NLRP3 inflammasome: key mediator of neuroinflammation in murine Japanese encephalitis. PLoS ONE7, e32270 (2012). ArticleCASPubMedPubMed Central Google Scholar
Masters, S. L. et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. Nature Immunol.11, 897–904 (2010). ArticleCAS Google Scholar
Nakahira, K. et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nature Immunol.12, 222–230 (2011). ArticleCAS Google Scholar
Zhou, R., Yazdi, A. S., Menu, P. & Tschopp, J. A role for mitochondria in NLRP3 inflammasome activation. Nature469, 221–225 (2011). ArticleCASPubMed Google Scholar
Subramanian, N., Natarajan, K., Clatworthy, M. R., Wang, Z. & Germain, R. N. The adaptor MAVS promotes NLRP3 mitochondrial localization and inflammasome activation. Cell153, 348–361 (2013). ArticleCASPubMedPubMed Central Google Scholar
Ramos, H. J. et al. IL-1β signaling promotes CNS-intrinsic immune control of West Nile virus infection. PLoS Pathog.8, e1003039 (2012). This study demonstrates a role for an inflammasome-dependent protective response during encephalitis caused by WNV. ArticleCASPubMedPubMed Central Google Scholar
Burguillos, M. A. et al. Caspase signalling controls microglia activation and neurotoxicity. Nature472, 319–324 (2011). ArticleCASPubMed Google Scholar
Shi, F. et al. The NALP3 inflammasome is involved in neurotoxic prion peptide-induced microglial activation. J. Neuroinflammation9, 73 (2012). ArticleCASPubMedPubMed Central Google Scholar
Hanamsagar, R., Torres, V. & Kielian, T. Inflammasome activation and IL-1β/IL-18 processing are influenced by distinct pathways in microglia. J. Neurochem.119, 736–748 (2011). ArticleCASPubMedPubMed Central Google Scholar
Gulbransen, B. D. et al. Activation of neuronal P2X7 receptor–pannexin-1 mediates death of enteric neurons during colitis. Nature Med.18, 600–604 (2012). ArticleCASPubMed Google Scholar
Kone-Paut, I. & Piram, M. Targeting interleukin-1β in CAPS (cryopyrin-associated periodic) syndromes: what did we learn? Autoimmun. Rev.12, 77–80 (2012). ArticleCASPubMed Google Scholar
Rathinam, V. A. et al. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nature Immunol.11, 395–402 (2010). ArticleCAS Google Scholar
Jin, T. et al. Structures of the HIN domain: DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor. Immunity36, 561–571 (2012). ArticleCASPubMedPubMed Central Google Scholar
Kummer, J. A. et al. Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response. J. Histochem. Cytochem.55, 443–452 (2007). ArticleCASPubMed Google Scholar
Yin, Y. et al. Inflammasomes are differentially expressed in cardiovascular and other tissues. Int. J. Immunopathol. Pharmacol.22, 311–322 (2009). ArticleCASPubMed Google Scholar
Guarda, G. et al. Differential expression of NLRP3 among hematopoietic cells. J. Immunol.186, 2529–2534 (2011). ArticleCASPubMed Google Scholar
Tarallo, V. et al. DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell149, 847–859 (2012). ArticleCASPubMedPubMed Central Google Scholar
Miggin, S. M. et al. NF-κB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1. Proc. Natl Acad. Sci. USA104, 3372–3377 (2007). ArticleCASPubMedPubMed Central Google Scholar
Agard, N. J., Maltby, D. & Wells, J. A. Inflammatory stimuli regulate caspase substrate profiles. Mol. Cell. Proteomics9, 880–893 (2010). ArticleCASPubMedPubMed Central Google Scholar
Griffin, W. S. et al. Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc. Natl Acad. Sci. USA86, 7611–7615 (1989). ArticleCASPubMedPubMed Central Google Scholar
McGuinness, M. C. et al. Human leukocyte antigens and cytokine expression in cerebral inflammatory demyelinative lesions of X-linked adrenoleukodystrophy and multiple sclerosis. J. Neuroimmunol.75, 174–182 (1997). ArticleCASPubMed Google Scholar
Zaremba, J. & Losy, J. Interleukin-18 in acute ischaemic stroke patients. Neurol. Sci.24, 117–124 (2003). ArticleCASPubMed Google Scholar
Taylor, R. C., Cullen, S. P. & Martin, S. J. Apoptosis: controlled demolition at the cellular level. Nature Rev. Mol. Cell Biol.9, 231–241 (2008). ArticleCAS Google Scholar
Lightfield, K. L. et al. Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin. Nature Immunol.9, 1171–1178 (2008). ArticleCAS Google Scholar
Lee, H. M. et al. Mycobacterium abscessus activates the NLRP3 inflammasome via Dectin-1-Syk and p62/SQSTM1. Immunol. Cell Biol.90, 601–610 (2012). ArticleCASPubMed Google Scholar
Soong, G., Chun, J., Parker, D. & Prince, A. Staphylococcus aureus activation of caspase 1/calpain signaling mediates invasion through human keratinocytes. J. Infect. Dis.205, 1571–1579 (2012). ArticleCASPubMedPubMed Central Google Scholar
Chien, H. & Dix, R. D. Evidence for multiple cell death pathways during development of experimental cytomegalovirus retinitis in mice with retrovirus-induced immunosuppression: apoptosis, necroptosis, and pyroptosis. J. Virol.86, 10961–10978 (2012). ArticleCASPubMedPubMed Central Google Scholar
Troy, C. M., Stefanis, L., Prochiantz, A., Greene, L. A. & Shelanski, M. L. The contrasting roles of ICE family proteases and interleukin-1β in apoptosis induced by trophic factor withdrawal and by copper/zinc superoxide dismutase down-regulation. Proc. Natl Acad. Sci. USA93, 5635–5640 (1996). ArticleCASPubMedPubMed Central Google Scholar
Guegan, C. et al. Instrumental activation of bid by caspase-1 in a transgenic mouse model of ALS. Mol. Cell. Neurosci.20, 553–562 (2002). ArticleCASPubMed Google Scholar
Friedlander, R. M. et al. Expression of a dominant negative mutant of interleukin-1 beta converting enzyme in transgenic mice prevents neuronal cell death induced by trophic factor withdrawal and ischemic brain injury. J. Exp. Med.185, 933–940 (1997). ArticleCASPubMedPubMed Central Google Scholar
Mehta, A., Prabhakar, M., Kumar, P., Deshmukh, R. & Sharma, P. L. Excitotoxicity: bridge to various triggers in neurodegenerative disorders. Eur. J. Pharmacol.698, 6–18 (2013). ArticleCASPubMed Google Scholar
McNeela, E. A. et al. Pneumolysin activates the NLRP3 inflammasome and promotes proinflammatory cytokines independently of TLR4. PLoS Pathog.6, e1001191 (2010). ArticleCASPubMedPubMed Central Google Scholar
Mitchell, A. J. et al. Inflammasome-dependent IFN-γ drives pathogenesis in Streptococcus pneumoniae meningitis. J. Immunol.189, 4970–4980 (2012). ArticleCASPubMed Google Scholar
Zwijnenburg, P. J. et al. Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis. J. Neuroimmunol.138, 31–37 (2003). ArticleCASPubMed Google Scholar
Lee, H. M., Kang, J., Lee, S. J. & Jo, E. K. Microglial activation of the NLRP3 inflammasome by the priming signals derived from macrophages infected with mycobacteria. Glia61, 441–452 (2013). ArticlePubMed Google Scholar
Kumar, M. et al. Inflammasome adaptor protein apoptosis-associated speck-like protein containing CARD (ASC) is critical for the immune response and survival in West Nile virus encephalitis. J. Virol.87, 3655–3667 (2013). ArticleCASPubMedPubMed Central Google Scholar
Mori, I. et al. Impaired microglial activation in the brain of IL-18-gene-disrupted mice after neurovirulent influenza A virus infection. Virology287, 163–170 (2001). ArticleCASPubMed Google Scholar
Sergerie, Y., Rivest, S. & Boivin, G. Tumor necrosis factor-α and interleukin-1β play a critical role in the resistance against lethal herpes simplex virus encephalitis. J. Infect. Dis.196, 853–860 (2007). ArticleCASPubMed Google Scholar
Schielke, G. P., Yang, G. Y., Shivers, B. D. & Betz, A. L. Reduced ischemic brain injury in interleukin-1β converting enzyme-deficient mice. J. Cereb. Blood Flow Metab.18, 180–185 (1998). ArticleCASPubMed Google Scholar
Wheeler, R. D. et al. No role for interleukin-18 in acute murine stroke-induced brain injury. J. Cereb. Blood Flow Metab.23, 531–535 (2003). ArticleCASPubMed Google Scholar
Pradillo, J. M. et al. Delayed administration of interleukin-1 receptor antagonist reduces ischemic brain damage and inflammation in comorbid rats. J. Cereb. Blood Flow Metab.32, 1810–1819 (2012). ArticleCASPubMedPubMed Central Google Scholar
Afonina, I. S. et al. Granzyme B-dependent proteolysis acts as a switch to enhance the proinflammatory activity of IL-1α. Mol. Cell44, 265–278 (2011). ArticleCASPubMedPubMed Central Google Scholar
Zheng, Y., Humphry, M., Maguire, J. J., Bennett, M. R. & Clarke, M. C. Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interleukin-1α, controlling necrosis-induced sterile inflammation. Immunity38, 285–295 (2013). ArticleCASPubMedPubMed Central Google Scholar
Keller, M., Ruegg, A., Werner, S. & Beer, H. D. Active caspase-1 is a regulator of unconventional protein secretion. Cell132, 818–831 (2008). ArticleCASPubMed Google Scholar
Abulafia, D. P. et al. Inhibition of the inflammasome complex reduces the inflammatory response after thromboembolic stroke in mice. J. Cereb. Blood Flow Metab.29, 534–544 (2009). ArticleCASPubMed Google Scholar
Frederick Lo, C., Ning, X., Gonzales, C. & Ozenberger, B. A. Induced expression of death domain genes NALP1 and NALP5 following neuronal injury. Biochem. Biophys. Res. Commun.366, 664–669 (2008). ArticleCASPubMed Google Scholar
Adamczak, S. et al. Inflammasome proteins in cerebrospinal fluid of brain-injured patients as biomarkers of functional outcome: clinical article. J. Neurosurg.117, 1119–1125 (2012). ArticleCASPubMedPubMed Central Google Scholar
Gris, D. et al. NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses. J. Immunol.185, 974–981 (2010). ArticleCASPubMed Google Scholar
Inoue, M., Williams, K. L., Gunn, M. D. & Shinohara, M. L. NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis. Proc. Natl Acad. Sci. USA109, 10480–10485 (2012). ArticlePubMedPubMed Central Google Scholar
Lalor, S. J. et al. Caspase-1-processed cytokines IL-1β and IL-18 promote IL-17 production by γδ and CD4 T cells that mediate autoimmunity. J. Immunol.186, 5738–5748 (2011). ArticleCASPubMed Google Scholar
Jha, S. et al. The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18. J. Neurosci.30, 15811–15820 (2010). This study shows that mice deficient in a particular inflammasome or caspase 1 activation pathway exhibit less neurological disease owing to an ameliorated inflammatory response. ArticleCASPubMedPubMed Central Google Scholar
Mason, J. L., Suzuki, K., Chaplin, D. D. & Matsushima, G. K. Interleukin-1β promotes repair of the CNS. J. Neurosci.21, 7046–7052 (2001). ArticleCASPubMedPubMed Central Google Scholar
Meissner, F., Molawi, K. & Zychlinsky, A. Mutant superoxide dismutase 1-induced IL-1β accelerates ALS pathogenesis. Proc. Natl Acad. Sci. USA107, 13046–13050 (2010). This study demonstrates that inflammasome activation in response to SOD1 enhances pathogenesis in an ALS model. ArticlePubMedPubMed Central Google Scholar
Craft, J. M., Watterson, D. M., Hirsch, E. & Van Eldik, L. J. Interleukin 1 receptor antagonist knockout mice show enhanced microglial activation and neuronal damage induced by intracerebroventricular infusion of human β-amyloid. J. Neuroinflammation2, 15 (2005). ArticleCASPubMedPubMed Central Google Scholar
Shaftel, S. S. et al. Sustained hippocampal IL-1β overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology. J. Clin. Invest.117, 1595–1604 (2007). ArticleCASPubMedPubMed Central Google Scholar
Heneka, M. T. et al. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature493, 674–678 (2013). This study shows that NLRP3 inflammasome activation adversely affects disease outcome in a mouse model of Alzheimer's disease. ArticleCASPubMed Google Scholar
Akhter, A. et al. Caspase-11 promotes the fusion of phagosomes harboring pathogenic bacteria with lysosomes by modulating actin polymerization. Immunity37, 35–47 (2012). ArticleCASPubMedPubMed Central Google Scholar
Rathinam, V. A. et al. TRIF licenses caspase-11-dependent NLRP3 inflammasome activation by Gram-negative bacteria. Cell150, 606–619 (2012). ArticleCASPubMedPubMed Central Google Scholar
Lu, J. X. et al. Molecular structure of β-amyloid fibrils in Alzheimer's disease brain tissue. Cell154, 1257–1268 (2013). ArticleCASPubMed Google Scholar
Yang, E. J., Kim, S., Kim, J. S. & Choi, I. H. Inflammasome formation and IL-1β release by human blood monocytes in response to silver nanoparticles. Biomaterials33, 6858–6867 (2012). ArticleCASPubMed Google Scholar
Liao, Y. H. et al. HMG-CoA reductase inhibitors activate caspase-1 in human monocytes depending on ATP release and P2X7 activation. J. Leukoc. Biol.93, 289–299 (2013). ArticleCASPubMed Google Scholar
Ruperto, N. et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N. Engl. J. Med.367, 2396–2406 (2012). ArticleCASPubMed Google Scholar
Coll, R. C. & O'Neill, L. A. The cytokine release inhibitory drug CRID3 targets ASC oligomerisation in the NLRP3 and AIM2 inflammasomes. PLoS ONE6, e29539 (2011). ArticleCASPubMedPubMed Central Google Scholar
Deroide, N. et al. MFGE8 inhibits inflammasome-induced IL-1β production and limits postischemic cerebral injury. J. Clin. Invest.123, 1176–1181 (2013). ArticleCASPubMedPubMed Central Google Scholar
Yan, Y. et al. Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation. Immunity38, 1154–1163 (2013). ArticleCASPubMed Google Scholar
Prinz, M., Priller, J., Sisodia, S. S. & Ransohoff, R. M. Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nature Neurosci.14, 1227–1235 (2011). ArticleCASPubMed Google Scholar
Hyman, B. T. & Yuan, J. Apoptotic and non-apoptotic roles of caspases in neuronal physiology and pathophysiology. Nature Rev. Neurosci.13, 395–406 (2012). ArticleCAS Google Scholar
Kaczmarek, A., Vandenabeele, P. & Krysko, D. V. Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity38, 209–223 (2013). ArticleCASPubMed Google Scholar
Chavez-Valdez, R., Martin, L. J., Flock, D. L. & Northington, F. J. Necrostatin-1 attenuates mitochondrial dysfunction in neurons and astrocytes following neonatal hypoxia-ischemia. Neuroscience219, 192–203 (2012). ArticleCASPubMed Google Scholar
Li, Z. et al. Caspase-3 activation via mitochondria is required for long-term depression and AMPA receptor internalization. Cell141, 859–871 (2010). ArticleCASPubMedPubMed Central Google Scholar
Graham, R. K., Ehrnhoefer, D. E. & Hayden, M. R. Caspase-6 and neurodegeneration. Trends Neurosci.34, 646–656 (2011). ArticleCASPubMed Google Scholar
Reimer, T. et al. Experimental cerebral malaria progresses independently of the Nlrp3 inflammasome. Eur. J. Immunol.40, 764–769 (2010). ArticleCASPubMedPubMed Central Google Scholar
Hafner-Bratkovic, I., Bencina, M., Fitzgerald, K. A., Golenbock, D. & Jerala, R. NLRP3 inflammasome activation in macrophage cell lines by prion protein fibrils as the source of IL-1β and neuronal toxicity. Cell. Mol. Life Sci.69, 4215–4228 (2012). ArticleCASPubMedPubMed Central Google Scholar