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Cited by 87Neuroinflammation and Neurodegeneration MechanismsPhagocytosis and Immune RegulationInflammasome and immune disorders

Microglial Immunoreceptor Tyrosine-Based Activation and Inhibition Motif Signaling in Neuroinflammation

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Linnartz, Bettina, Wang, Yiner, Neumann, Harald·2010·International Journal of Alzheimer's Disease
DOI 10.4061/2010/587463PMC PMC2915791
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Abstract

Elimination of extracellular aggregates and apoptotic neural membranes without inflammation is crucial for brain tissue homeostasis. In the mammalian central nervous system, essential molecules in this process are the Fc receptors and the DAP12-associated receptors which both trigger the microglial immunoreceptor tyrosine-based activation motif- (ITAM-) Syk-signaling cascade. Microglial triggering receptor expressed on myeloid cells-2 (TREM2), signal regulatory protein-1, and complement receptor-3 (CD11b/CD18) signal via the adaptor protein DAP12 and activate phagocytic activity of microglia. Microglial ITAM-signaling receptors are counter-regulated by immunoreceptor tyrosine-based inhibition motif- (ITIM-) signaling molecules such as sialic acid-binding immunoglobulin superfamily lectins (Siglecs). Siglecs can suppress the proinflammatory and phagocytic activity of microglia via ITIM signaling. Moreover, microglial neurotoxicity is alleviated via interaction of Siglec-11 with sialic acids on the neuronal glycocalyx. Thus, ITAM- and ITIM-signaling receptors modulate microglial phagocytosis and cytokine expression during neuroinflammatory processes. Their dysfunction could lead to impaired phagocytic clearance and neurodegeneration triggered by chronic inflammation.

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Cited by

Sorted by citations

Authors
Linnartz, B., Wang, Y., & Neumann, H.
Affiliations
  • Neural Regeneration, Institute of Reconstructive Neurobiology, University Hospital Bonn, University Bonn, 53127 Bonn, Germany
  • University of Bonn (DE)
Corresponding author
Neumann, Harald
ORCID
Neumann, Harald
Venue
International Journal of Alzheimer's Disease
Publisher
Hindawi Limited
Published
2010
Volume
2010
Pages
1-7
ISSN
2090-0252 (ISSN-L)
DOI
10.4061/2010/587463
PMC
PMC2915791
OpenAlex
W2071805913
Cited by
87
References
18
Citations by year
2025: 3 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 4 · 2020: 11 · 2019: 7 · 2018: 4 · 2017: 5 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 6 · 2012: 8
FWCI
3.54
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Alzheimer s Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Deutsche Forschungsgemeinschaft (KFO177, SFB 704, DFG‐SFB704, DFG-FOR1336, FOR1336, DFG KFO177)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords
microglia, neuroinflammation, ITAM signaling, DAP12, Syk signaling, TREM2, Siglecs, sialic acid, phagocytosis, Fc receptors, CD11b/CD18, neurodegeneration, cytokine expression

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