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Nat Rev Immunol. 2014 Jul;14(7):463-77. doi: 10.1038/nri3705.

Innate immune activation in neurodegenerative disease.

Author information

1
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.
2
Clinical Neuroscience, Department of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
3
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.

Abstract

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.

PMID:
24962261
DOI:
10.1038/nri3705
[Indexed for MEDLINE]

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