Inflammasome activation and innate immunity in Alzheimer's disease.

NLRP3; cytokine; danger associated molecular pattern; microglia; neuroinflammation; Carrier Proteins; Inflammasomes; Interleukin-1beta; NLR Family, Pyrin Domain-Containing 3 Protein; Nod-like receptor protein 3 inflammasome, mouse; Receptors, Cell Surface; Alzheimer Disease/pathology; Animals; Brain/pathology; Carrier Proteins/metabolism; Disease Models, Animal; Humans; Immunity, Innate/immunology; Inflammasomes/metabolism; Interleukin-1beta/metabolism; Mice; Microglia/pathology; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism; NLR Family, Pyrin Domain-Containing 3 Protein/physiology; Receptors, Cell Surface/metabolism; Alzheimer Disease; Brain; Immunity, Innate; Neuroscience (all); Pathology and Forensic Medicine; Neurology (clinical); General Neuroscience

Abstract :

[en] Activation of innate immunity and the assembly of microglial cells at sites of Alzheimer disease pathology has long been regarded as bystander phenomenon, which does not actively contribute to disease pathogenesis and progression. Recent data emerging from genetics, clinical imaging and animal experimentation point to an intimate and mutual interaction of innate immune mechanisms and neurodegenerative processes. NOD-like receptor (NLR) family, pyrin domain containing 3 and 1 inflammasomes, present in myeloid cells and neurons, respectively, represent key components of the innate immune reaction observed in Alzheimer patient brains. Inhibition of inflammasome activation just begins to prove beneficial and protective from cognitive deficits and neuronal death in cell culture and animal models of Alzheimer's disease, thereby opening a new avenue for therapeutic intervention.

Disciplines :

Neurology

Author, co-author :

HENEKA, Michael ; Department of Neurodegenerative Disease, University of Bonn, Bonn, Germany ; German Center for Neurodegenerative Disease, Bonn, Germany

External co-authors :

yes

Language :

English

Title :

Inflammasome activation and innate immunity in Alzheimer's disease.

Publication date :

March 2017

Journal title :

Brain Pathology

ISSN :

1015-6305

Publisher :

Blackwell Publishing Ltd, Switzerland

Volume :

Issue :

Pages :

220 - 222

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fbpa.12483

Available on ORBilu :

since 08 May 2024

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119

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Bibliography

Chapman MR, Robinson LS, Pinkner JS, Roth R, Heuser J, Hammar M et al (2002) Role of Escherichia coli curli operons in directing amyloid fiber formation. Science 295:851–855.
Chen L, Na R, Boldt E, Ran Q (2015) NLRP3 inflammasome activation by mitochondrial reactive oxygen species plays a key role in long-term cognitive impairment induced by paraquat exposure. Neurobiol Aging 36:2533–2543.
Couturier J, Stancu IC, Schakman O, Pierrot N, Huaux F, Kienlen-Campard P et al (2016) Activation of phagocytic activity in astrocytes by reduced expression of the inflammasome component ASC and its implication in a mouse model of Alzheimer disease. J Neuroinflamm 13:20.
Cribbs DH, Berchtold NC, Perreau V, Coleman PD, Rogers J, Tenner AJ, Cotman CW (2012) Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study. J Neuroinflamm 9:179.
Daniels MJD, Rivers-Auty J, Schilling T, Spencer NG, Watremez W, Fasolino V et al (2016) Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer's disease in rodent models. Nat Commun 7:12504.
Franklin BS, Bossaller L, De Nardo D, Ratter JM, Stutz A, Engels G et al (2014) The adaptor ASC has extracellular and “prionoid” activities that propagate inflammation. Nat Immunol 15:727–737.
Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T et al (2008) The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol 9:857–865.
Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A et al (2013) NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 493:674–678.
Heneka MT, Golenbock DT, Latz E (2015) Innate immunity in Alzheimer's disease. Nat Immunol 16:229–236.
Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS et al (2013) Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 12:207–216.
Kaushal V, Dye R, Pakavathkumar P, Foveau B, Flores J, Hyman B et al (2015) Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation. Cell Death Differ 22:1676–1686.
Sheedy FJ, Grebe A, Rayner KJ, Kalantari P, Ramkhelawon B, Carpenter SB et al (2013) CD36 coordinates NLRP3 inflammasome activation by facilitating the intracellular nucleation from soluble to particulate ligands in sterile inflammation. Nat Immunol 14:812–820.
Shi JQ, Zhang CC, Sun XL, Cheng XX, Wang JB, Zhang YD et al (2013) Antimalarial drug artemisinin extenuates amyloidogenesis and neuroinflammation in APPswe/PS1dE9 transgenic mice via inhibition of nuclear factor-κB and NLRP3 inflammasome activation. CNS Neurosci Ther 19:262–268.
Tan MS, Tan L, Jiang T, Zhu XC, Wang HF, Jia CD, Yu JT (2014) Amyloid-β induces NLRP1-dependent neuronal pyroptosis in models of Alzheimer's disease. Cell Death Dis 5:e1382.
Wu Z, Sun L, Hashioka S, Yu S, Schwab C, Okada R et al (2013) Differential pathways for interleukin-1β production activated by chromogranin A and amyloid β in microglia. Neurobiol Aging 34:2715–2725.
Leissring MA, Farris W, Chang AY, Walsh DM, Wu X, Sun X, Frosch MP, Selkoe DJ (2003) Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron 40:1087–1093.