Intracellular C1q—an unexpected player in neuronal proteostasis
Open accessAbstract
Extrahepatic, cell-autonomous, and/or intracellularly active complement components are increasingly recognized as key orchestrators of cell physiological processes. A recent study by Scott-Hewitt et al. demonstrates that microglia-derived C1q unexpectedly associates with the ribosomes of neurons in the aging murine brain, where it impacts protein translation and impairs the extinction of conditioned fear responses.
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ST analysis found a significant increase in RNA expression of C1QB.
“These findings were confirmed in the ST analysis where we found a significant increase in RNA expression of C1QB, a protein directly associated with brain ribosomal function and protein synthesis. 57”
From Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations (2026) · cites this paper as [57]
The paper’s Abstract links C1q to neuronal ribosomes and reports effects on protein translation, supporting the cited functional association. It does not identify C1QB specifically. The significant increase in C1QB RNA is presented as the citing authors’ own ST finding, not as a result from this source. (LLM, conf=0.82)
Experimental — accuracy not yet measuredC1QB is directly associated with brain ribosomal function and protein synthesis.
“These findings were confirmed in the ST analysis where we found a significant increase in RNA expression of C1QB, a protein directly associated with brain ribosomal function and protein synthesis. 57”
From Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations (2026) · cites this paper as [57]
The paper’s Abstract describes C1q interacting with neuronal ribonucleoprotein complexes and ribosomes and affecting protein translation in aging mice. It does not identify C1QB specifically as the protein responsible, so the claim is more specific than the cited evidence. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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Cites
Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343 · see citing works
The Classical Complement Cascade Mediates CNS Synapse Elimination
Stevens, B., Allen, N. J., Vazquez, L. E., Howell, G. R., Christopherson, K. S., Nouri, N., Micheva, K. D., Mehalow, A. K., Huberman, A. D., Stafford, B., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.036 · Cited by 3,313 · see citing works
A Dramatic Increase of C1q Protein in the CNS during Normal Aging
Stephan, A. H., Madison, D. V., Mateos, J. M., Fraser, D. A., Lovelett, E. A., Coutellier, L., Kim, L., Tsai, H.-H., Huang, E. J., Rowitch, D. H., et al. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1333-13.2013 · Cited by 423 · see citing works
Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease
Fonseca, M. I., Zhou, J., Botto, M., & Tenner, A. J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0901-04.2004 · Cited by 345 · see citing works
Dejanovic, B., Wu, T., Tsai, M.-C., Graykowski, D., Gandham, V. D., Rose, C. M., Bakalarski, C. E., Ngu, H., Wang, Y., Pandey, S., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00281-1 · Cited by 341 · see citing works
Cell-specific deletion of C1qa identifies microglia as the dominant source of C1q in mouse brain
Fonseca, M. I., Chu, S.-H., Hernandez, M. X., Fang, M. J., Modarresi, L., Selvan, P., MacGregor, G. R., & Tenner, A. J. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0814-9 · Cited by 337 · see citing works
Complosome — the intracellular complement system
West, E. E., & Kemper, C. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00704-1 · Cited by 256 · see citing works
Self-citationC1q restrains autoimmunity and viral infection by regulating CD8 <sup>+</sup> T cell metabolism
Ling, G. S., Crawford, G., Buang, N., Bartok, I., Tian, K., Thielens, N. M., Bally, I., Harker, J. A., Ashton-Rickardt, P. G., Rutschmann, S., et al. (2018) · Science · doi:10.1126/science.aao4555 · Cited by 199 · see citing works
Benoit, M. E., & Tenner, A. J. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3932-10.2011 · Cited by 160 · see citing works
Benoit, M. E., Hernandez, M. X., Dinh, M. L., Benavente, F., Vasquez, O., & Tenner, A. J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.400168 · Cited by 155 · see citing works
Scott‐Hewitt, N., Mahoney, M., Huang, Y., Korte, N., de Soysa, Y., Wilton, D. K., Knorr, E., Mastro, K. J., Chang, A., Zhang, A., et al. (2024) · Cell · doi:10.1016/j.cell.2024.05.058 · Cited by 89 · see citing works
Novel C1q receptor-mediated signaling controls neural stem cell behavior and neurorepair
Benavente, F., Piltti, K. M., Hooshmand, M. J., Nava, A. A., Lakatos, A., Feld, B. G., Creasman, D. A., Gershon, P. D., & Anderson, A. J. (2020) · eLife · doi:10.7554/elife.55732 · Cited by 33 · see citing works
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Microglia and neuroinflammation: function, heterogeneity, and crosstalk
Zong, S., Cui, X., Wu, S., & Lu, Z. (2026) · Cellular and Molecular Immunology · doi:10.1038/s41423-026-01438-3 · Cited by 24 · see citing works
Ye, Q., Gao, W., Feng, J., Li, X., Li, J., Yang, F., Li, L., Zi, M., Wu, X., Gao, H., et al. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71185 · Cited by 11 · see citing works
The complement cascade in Alzheimer’s disease: modern implications of an ancient immune protagonist
Papavergi, M.-T., Bathini, P., Singh, B. B., & Lemere, C. A. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00916-y · Cited by 10 · see citing works
Firdaus, N. H. W., Mallick, B., Nandakumar, K. S., & Shakya, A. K. (2025) · Journal of The Royal Society Interface · doi:10.1098/rsif.2025.0138 · Cited by 2 · see citing works
Nordbeck, A. J., Martá‐Ariza, M., Ek Olofsson, H., Kanshin, E., Ueberheide, B., Jones, K., Sanford, B., Hamlett, E. D., Head, E., Mufson, E. J., et al. (2026) · Alzheimer's & Dementia · doi:10.1002/alz.71776
“57 This was particularly evident in CA1/CA2 neurons, which are vulnerable to AD pathology.”
- Authors
- West, E. E., & Kemper, C.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- West, Erin E.
- Kemper, Claudia
- ORCID
- Kemper, Claudia
- Venue
- Trends in Immunology
- Publisher
- Elsevier BV
- Published
- 2024-10
- Volume
- 45
- Issue
- 10
- Pages
- 718-720
- ISSN
- 1471-4906 (ISSN-L)
- PMC
- PMC12163964
- OpenAlex
- W4402848077
- Cited by
- 5
- References
- 12
- Citations by year
- 2026: 3 · 2025: 2
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Trends in Immunology (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute
- National Institutes of Health
- National Heart Lung and Blood Institute Division of Intramural Research (ZIA/hl006223)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Keywords
- complement system, neuronal proteostasis, microglia, ribosome, mRNA translation, brain aging, neurodegeneration
- MeSH terms
- Proteostasis, Aging, Animals, Brain, Humans, Neurons, Ribosomes, Protein Biosynthesis, Complement C1q, Microglia, Mice
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