Cited by 335Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsAtherosclerosis and Cardiovascular Diseases

A CD36-initiated Signaling Cascade Mediates Inflammatory Effects of β-Amyloid

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Moore, Kathryn J., El Khoury, Joseph, Medeiros, Lea A., Terada, Kinya, Geula, Changiz, Luster, Andrew D., Freeman, Mason W.·2002·Journal of Biological Chemistry

Abstract

beta-Amyloid accumulation is associated with pathologic changes in the brain in Alzheimer's disease and has recently been identified in plaques of another chronic inflammatory disorder, atherosclerosis. The class B scavenger receptor, CD36, mediates binding of fibrillar beta-amyloid to cells of the monocyte/macrophage lineage, including brain macrophages (microglia). In this study, we demonstrate that in microglia and other tissue macrophages, beta-amyloid initiates a CD36-dependent signaling cascade involving the Src kinase family members, Lyn and Fyn, and the mitogen-activated protein kinase, p44/42. Interruption of this signaling cascade, through targeted disruption of Src kinases downstream of CD36, inhibits macrophage inflammatory responses to beta-amyloid, including reactive oxygen and chemokine production, and results in decreased recruitment of microglia to sites of amyloid deposition in vivo. The finding that engagement of CD36 by beta-amyloid initiates a Src kinase-dependent production of inflammatory mediators in cells of the macrophage lineage reveals a novel receptor-mediated pro-inflammatory signaling pathway of potential therapeutic importance.

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Crossref · 10.1074/jbc.m208788200

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Authors
Moore, K. J., El Khoury, J., Medeiros, L. A., Terada, K., Geula, C., Luster, A. D., & Freeman, M. W.
Affiliations
  • Harvard University (US)
  • Beth Israel Deaconess Medical Center (US)
Corresponding author
Freeman, Mason W.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2002-12
Volume
277
Issue
49
Pages
47373-47379
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2106020004
Cited by
327
References
32
Citations by year
2026: 2 · 2025: 6 · 2024: 7 · 2023: 10 · 2022: 14 · 2021: 18 · 2020: 17 · 2019: 13 · 2018: 10 · 2017: 10 · 2016: 15 · 2015: 19 · 2014: 8 · 2013: 18 · 2012: 20
FWCI
8.21
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (R01AG020255, R01AG20255-01)
  • National Heart, Lung, and Blood Institute (R01 HL45098, R01HL045098)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P01-DK50305, P01DK050305)
  • National Institute of Neurological Disorders and Stroke (NS41330-02, K08NS041330)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords
amyloid-beta, CD36, scavenger receptors, microglia, macrophages, Src kinase, Lyn kinase, Fyn, receptor signaling, neuroinflammation, reactive oxygen species, chemokine production, microglial recruitment, Alzheimer's disease, atherosclerosis, amyloid plaques
MeSH terms
Alleles, Animals, Brain, Crosses, Genetic, Female, Immunohistochemistry, Inflammation, Leukocytes, Mononuclear, Ligands, Macrophages, Mice, Inbred C57BL, Models, Biological, Phosphorylation, Precipitin Tests, Proto-Oncogene Proteins, Tyrosine, Blotting, Western, Signal Transduction, Amyloid beta-Peptides, Reactive Oxygen Species, Microglia, Mice, Knockout, CD36 Antigens, src-Family Kinases, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, Proto-Oncogene Proteins c-fyn, Mice

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