The DOI matches its Crossref record; 30 of the 32 references it cites were found in a registry or an index.
A CD36-initiated Signaling Cascade Mediates Inflammatory Effects of β-Amyloid
Open accessAbstract
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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“Through these additional substrates, BACE1 has been implicated in inflammation, cardiovascular function, glucose homeostasis, and insulin signaling”
From BACE1: More than just a β‐secretase (2022) · cites this paper as [35]
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“Furthermore, CD36 mediates fAβ-induced signal cascade which leads to the production of ROS and chemokines [366].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [366]
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The NALP3 inflammasome is involved in the innate immune response to amyloid-β
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Metadata
- 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
- hybrid
- doi.org
- Licence
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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