Activated Cyclin-Dependent Kinase 5 Promotes Microglial Phagocytosis of Fibrillar β-Amyloid by Up-regulating Lipoprotein Lipase Expression
Open accessAbstract
Amyloid plaques are crucial for the pathogenesis of Alzheimer disease (AD). Phagocytosis of fibrillar β-amyloid (Aβ) by activated microglia is essential for Aβ clearance in Alzheimer disease. However, the mechanism underlying Aβ clearance in the microglia remains unclear. In this study, we performed stable isotope labeling of amino acids in cultured cells for quantitative proteomics analysis to determine the changes in protein expression in BV2 microglia treated with or without Aβ. Among 2742 proteins identified, six were significantly up-regulated and seven were down-regulated by Aβ treatment. Bioinformatic analysis revealed strong over-representation of membrane proteins, including lipoprotein lipase (LPL), among proteins regulated by the Aβ stimulus. We verified that LPL expression increased at both mRNA and protein levels in response to Aβ treatment in BV2 microglia and primary microglial cells. Silencing of LPL reduced microglial phagocytosis of Aβ, but did not affect degradation of internalized Aβ. Importantly, we found that enhanced cyclin-dependent kinase 5 (CDK5) activity by increasing p35-to-p25 conversion contributed to LPL up-regulation and promoted Aβ phagocytosis in microglia, whereas inhibition of CDK5 reduced LPL expression and Aβ internalization. Furthermore, Aβ plaques was increased with reducing p25 and LPL level in APP/PS1 mouse brains, suggesting that CDK5/p25 signaling plays a crucial role in microglial phagocytosis of Aβ. In summary, our findings reveal…
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Microglial LPL expression has been implicated in brain development, damage, and disease.
“Moreover, microglial LPL expression has been implicated in brain development, damage, and disease [25,26,27].”
From Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation (2021) · cites this paper as [26]
The Results and Discussion (page unavailable in our copy) link microglial LPL expression to amyloid-β clearance and Alzheimer’s disease. They do not establish a role for microglial LPL expression in brain development or damage, so this source supports only the disease portion of the claim. (LLM, conf=0.86)
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- Authors
- Ma, Y., Bao, J., Zhao, X., Shen, H., Lv, J., Ma, S., Zhang, X., Li, Z., Wang, S., Wang, Q., & Ji, J.
- Affiliations
- Peking University (CN)
- Corresponding author
- Wang, Qingsong
- Ji, Jianguo
- ORCID
- Venue
- Molecular & Cellular Proteomics
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 12
- Issue
- 10
- Pages
- 2833-2844
- ISSN
- 1535-9476 (ISSN-L)
- PMC
- PMC3790294
- OpenAlex
- W1978661028
- Semantic Scholar
- b3528758a88121cd3f6fbf7ecc66e37916a7e439
- Cited by
- 60
- References
- 58
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 9 · 2020: 7 · 2019: 6 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 5 · 2014: 4
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular & Cellular Proteomics (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 › Phagocytosis and Immune Regulation
- Keywords
- cyclin-dependent kinase 5, lipoprotein lipase, microglial phagocytosis, amyloid plaque clearance, Alzheimer's disease, microglia, APP/PS1 mice, protein expression profiling, BV-2 cells
- MeSH terms
- Animals, Cell Line, Cells, Cultured, Lipoprotein Lipase, Phagocytosis, Up-Regulation, Amyloid beta-Peptides, Rats, Sprague-Dawley, Microglia, Cyclin-Dependent Kinase 5, Mice, Rats
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