Clusterin
Abstract
Clusterin is an enigmatic glycoprotein with a nearly ubiquitous tissue distribution and an apparent involvement in biological processes ranging from mammary gland involution to neurodegeneration in Alzheimer's disease. Its major form, a 75-80 kDa heterodimer, is secreted and present in physiological fluids, but truncated forms targeted to the nucleus have also been identified. Upregulation of clusterin mRNA and protein levels detected in diverse disease states and in in vitro systems have led to suggestions that it functions in membrane lipid recycling, in apoptotic cell death, and as a stress-induced secreted chaperone protein, amongst others. Recent studies of knockout mice have further complicated the picture by implicating clusterin in exacerbating neuronal death in hypoxia-ischemia. The question of whether clusterin is a multifunctional protein, or deploys a single primary function influenced by cellular context, remains a central issue continuing to stimulate interest in this unusual molecule.
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CLU levels are elevated in a number of pathological conditions involving injury or chronic inflammation of the brain.
“there is strong evidence that CLU levels are elevated in a number of pathological conditions involving injury or chronic inflammation of the brain 17 .”
From Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease (2009) · cites this paper as [17]
In Alzheimer's disease brain, CLU expression is increased in affected cortical areas and is present in amyloid plaques and cerebrospinal fluid of AD cases.
“In Alzheimer's disease brain, CLU expression is reported to be increased in affected cortical areas and is present in amyloid plaques and in the cerebrospinal fluid of AD cases [17][18][19][20] .”
From Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease (2009) · cites this paper as [17]
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Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326 · see citing works
Neuroinflammation in Alzheimer's disease: current evidence and future directions
Calsolaro, V., & Edison, P. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.02.010 · Cited by 1,726 · see citing works
Alzheimer’s Disease Risk Genes and Mechanisms of Disease Pathogenesis
Karch, C. M., & Goate, A. M. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.05.006 · Cited by 1,357 · see citing works
Clusterin in Alzheimer’s Disease: Mechanisms, Genetics, and Lessons From Other Pathologies
Foster, E. M., Dangla-Valls, A., Lovestone, S., Ribe, E. M., & Buckley, N. J. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00164 · Cited by 381 · see citing works
Genes associated with Alzheimer's disease: an overview and current status
Giri, M., Lü, Y., & Zhang, M. (2016) · Clinical Interventions in Aging · doi:10.2147/cia.s105769 · Cited by 311 · see citing works
Characterization and functional consequences of underexpression of clusterin in rheumatoid arthritis
Devauchelle, V., Essabbani, A., De Pinieux, G., Germain, S., Tourneur, L., Mistou, S., Margottin-Goguet, F., Anract, P., Migaud, H., Le Nen, D., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.9.6471 · Cited by 78 · see citing works
Sustained astrocytic clusterin expression improves remodeling after brain ischemia
Imhof, A., Charnay, Y., Vallet, P. G., Aronow, B., Kovari, E., French, L. E., Bouras, C., & Giannakopoulos, P. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.11.009 · Cited by 73 · see citing works
Apolipoprotein J (clusterin) activates rodent microglia <i>in vivo</i> and <i>in vitro</i>
Xie, Z., Harris‐White, M. E., Wals, P. A., Frautschy, S. A., Finch, C. E., & Morgan, T. E. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03065.x · Cited by 53 · see citing works
A model for modulation of leptin activity by association with clusterin
Bajari, T. M., Strasser, V., Nimpf, J., & Schneider, W. J. (2003) · The FASEB Journal · doi:10.1096/fj.02-1106fje · Cited by 45 · see citing works
Differential effects of apoE4 and activation of ABCA1 on brain and plasma lipoproteins
Boehm-Cagan, A., Bar, R., Harats, D., Shaish, A., Levkovitz, H., Bielicki, J. K., Johansson, J. O., & Michaelson, D. M. (2016) · PLOS ONE · doi:10.1371/journal.pone.0166195 · Cited by 29 · see citing works
Kashyap, M. P., Khan, J., Sinha, R., Jin, L., Atigadda, V., Deshane, J. S., Ahmed, A. R., Kilic, A., Raman, C., Mukhtar, M. S., et al. (2022) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2022.01.006 · Cited by 22 · see citing works
- Authors
- Jones, S.
- Affiliations
- St Thomas' Hospital (GB)
- Corresponding author
- Jones, S
- Venue
- The International Journal of Biochemistry & Cell Biology
- Publisher
- Elsevier BV
- Published
- 2002-05
- Volume
- 34
- Issue
- 5
- Pages
- 427-431
- ISSN
- 1357-2725 (ISSN-L)
- OpenAlex
- W4245265700
- Cited by
- 488
- References
- 0
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 17 · 2023: 15 · 2022: 25 · 2021: 13 · 2020: 22 · 2019: 18 · 2018: 19 · 2017: 20 · 2016: 28 · 2015: 29 · 2014: 26 · 2013: 29 · 2012: 24
- FWCI
- 8.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The International Journal of Biochemistry & Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Clusterin in disease pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Keywords
- clusterin, glycoproteins, heterodimer, apoptosis, molecular chaperones, hypoxia-ischemia, neuronal cell death, Alzheimer's disease, mammary gland involution, knockout mice, multifunctional proteins
- MeSH terms
- Animals, Glycoproteins, Humans, Models, Biological, Neoplasm Proteins, Protein Structure, Secondary, Molecular Chaperones, Clusterin
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