[en] The triggering of innate immune mechanisms is emerging as a crucial component of major neurodegenerative diseases. Microglia and other cell types in the brain can be activated in response to misfolded proteins or aberrantly localized nucleic acids. This diverts microglia from their physiological and beneficial functions, and leads to their sustained release of pro-inflammatory mediators. In this Review, we discuss how the activation of innate immune signalling pathways - in particular, the NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome - by aberrant host proteins may be a common step in the development of diverse neurodegenerative disorders. During chronic activation of microglia, the sustained exposure of neurons to pro-inflammatory mediators can cause neuronal dysfunction and contribute to cell death. As chronic neuroinflammation is observed at relatively early stages of neurodegenerative disease, targeting the mechanisms that drive this process may be useful for diagnostic and therapeutic purposes.
Disciplines :
Neurologie
Auteur, co-auteur :
HENEKA, Michael ; 1] Clinical Neuroscience, Department of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany. [2] Department of Internal Medicine, University of Massachusetts, Worcester, Massachusetts 01605, USA. [3] German Center for Neurodegenerative Diseases (DZNE), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany
Kummer, Markus P; Clinical Neuroscience, Department of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany
Latz, Eicke; 1] Department of Internal Medicine, University of Massachusetts, Worcester, Massachusetts 01605, USA. [2] German Center for Neurodegenerative Diseases (DZNE), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany. [3] Institute of Innate Immunity, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany
Co-auteurs externes :
yes
Langue du document :
Anglais
Titre :
Innate immune activation in neurodegenerative disease.
Date de publication/diffusion :
juillet 2014
Titre du périodique :
Nature Reviews. Immunology
ISSN :
1474-1733
eISSN :
1474-1741
Maison d'édition :
Nature Publishing Group, Basingstoke, Hampshire, England
The authors’ work was supported by grants to M.T.H. and E.L. from the German Research Council (Deutsche Forschungsgemeinschaft, KFO177 and Cluster of Excellence “Immunosensation”).
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