Affinage

CLU

Clusterin · UniProt P10909

Length
449 aa
Mass
52.5 kDa
Annotated
2026-04-28
100 papers in source corpus 19 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLU (clusterin/apolipoprotein J/SP-40,40) is a secreted heterodimeric glycoprotein chaperone that functions as a broad extracellular proteostasis and cytoprotective factor, with roles spanning complement regulation, lipoprotein metabolism, amyloid-beta clearance, and neuroinflammatory control. The mature protein is generated by proteolytic cleavage of a single-chain precursor into disulfide-linked alpha and beta chains arranged in a unique antiparallel disulfide ladder; mutations in the beta-chain disulfide region cause ER retention and loss of secretion (PMID:2721499, PMID:1551440, PMID:26179372). Extracellularly, sCLU inhibits complement membrane-attack complex assembly by sequestering nascent C5b-7, associates with HDL, complexes soluble amyloid-beta in CSF, activates AKT survival signaling, and is internalized by microglia via TREM2 (PMID:2454950, PMID:1903064, PMID:8328966, PMID:22012253, PMID:27477018). In astrocytes, CLU suppresses NF-κB/complement C3-dependent inflammatory signaling to limit microglial synaptic phagocytosis, with its expression regulated by TDP-43 binding at the AD-risk SNP rs11136000 and epigenetically silenced by EZH2-mediated H3K27 trimethylation (PMID:40311610, PMID:37494190, PMID:22068036).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1988 High

    Establishing CLU's first known function: the question of what SP-40,40 does in serum was answered by showing it inhibits complement-mediated cytolysis by incorporating into the soluble membrane-attack complex and inactivating nascent C5b-7.

    Evidence Protein purification, hemolysis inhibition assay, and immunodepletion/reconstitution of SC5b-9 from human serum

    PMID:2150757 PMID:2454950 PMID:2489042

    Open questions at the time
    • Structural basis of C5b-7 recognition unknown
    • In vivo complement-regulatory role not demonstrated at this point
    • Stoichiometry of SP-40,40 in SC5b-9 complex not fully defined
  2. 1989 High

    The biosynthetic origin of CLU's two-chain structure was resolved: a single mRNA encodes both alpha and beta chains as a precursor that undergoes post-translational cleavage and N-linked glycosylation for secretory export.

    Evidence cDNA cloning and full-length sequence analysis from human liver

    PMID:2721499

    Open questions at the time
    • Identity of the processing protease unknown
    • Signals governing glycosylation site occupancy not characterized
  3. 1991 Medium

    Two new biological contexts for CLU were established: association with HDL in plasma implicated CLU in lipoprotein metabolism, and its dynamic binding/release cycle on spermatozoa in the epididymis revealed a role in reproductive biology.

    Evidence FPLC/immunoaffinity chromatography of plasma lipoproteins; micropuncture/microperfusion and 2D Western blot of epididymal luminal fluid

    PMID:1781989 PMID:1903064

    Open questions at the time
    • Functional consequence of HDL association for lipid transport unclear
    • Whether CLU on spermatozoa influences fertilization not tested
    • Receptor mediating epididymal re-uptake unknown
  4. 1992 High

    The unique disulfide architecture of CLU was mapped: all 10 cysteines form interchain alpha–beta bonds in an antiparallel ladder, with no free sulfhydryls, establishing a structural hallmark distinct from other complement-associated proteins.

    Evidence Tryptic peptide mapping, HPLC, amino acid sequencing of disulfide peptides

    PMID:1491011 PMID:1551440

    Open questions at the time
    • No three-dimensional structure available
    • Functional role of individual disulfide bonds not dissected
  5. 1993 High

    CLU was linked to Alzheimer's disease biology by demonstrating that soluble amyloid-beta in CSF is physically complexed with CLU, establishing CLU as an endogenous Aβ-binding chaperone.

    Evidence Direct binding assay with synthetic Aβ peptide and co-immunoprecipitation from human CSF

    PMID:8328966

    Open questions at the time
    • Whether CLU-Aβ complexation prevents or promotes amyloid deposition in vivo unknown
    • Binding stoichiometry and affinity not quantified
    • Receptor-mediated clearance of CLU-Aβ complex not identified
  6. 1999 Medium

    Extracellular CLU was shown to confer cytoprotection against TNF-induced cell death: neutralizing secreted CLU sensitized resistant cancer cells to TNF, and exogenous CLU reversed this effect.

    Evidence Antibody neutralization of secreted CLU, exogenous protein rescue, cell viability assay in prostate cancer lines

    PMID:10221563

    Open questions at the time
    • Downstream signaling pathway mediating anti-TNF effect not identified
    • Whether this reflects a general anti-apoptotic function or TNF-specific mechanism unclear
  7. 2002 Medium

    A direct anti-proliferative function for CLU was demonstrated: overexpression caused G0/G1 arrest, reduced DNA synthesis, and upregulated growth arrest gene Gas1, extending CLU's role beyond secreted chaperone to cell-autonomous growth regulation.

    Evidence Transient transfection in PNT2 prostate epithelial cells, flow cytometry, thymidine incorporation, enzyme activity assays

    PMID:12082621

    Open questions at the time
    • Mechanism linking CLU to Gas1 upregulation unknown
    • Whether the anti-proliferative effect requires secreted or intracellular CLU not distinguished
  8. 2011 High

    Two studies resolved how CLU expression is regulated and how its secreted vs. intracellular forms differ functionally: EZH2 directly silences CLU via H3K27me3, while sCLU activates AKT and intracellular CLU inhibits NF-κB in a complex with HSP60.

    Evidence ChIP for H3K27me3/PRC2 at CLU locus with EZH2 knockdown/knockout; Co-IP of CLU-HSP60, AKT activity assay, NF-κB reporter assay in neuroblastoma cells

    PMID:22012253 PMID:22068036

    Open questions at the time
    • Identity of kinase(s) downstream of sCLU-AKT activation unknown
    • Physiological relevance of CLU-HSP60 complex outside neuroblastoma not tested
    • Whether EZH2-mediated silencing operates in neurons or astrocytes unknown
  9. 2015 High

    The functional requirement of the beta-chain disulfide region for CLU secretion was demonstrated: patient-derived mutations in this region cause ER retention and abolish heterodimerization, linking structural integrity to secretory pathway transit.

    Evidence Expression of three CLU point mutants in HEK293T/Flp-In cells, ICC co-localization with ER markers, ELISA for secreted CLU

    PMID:26179372

    Open questions at the time
    • Whether ER-retained CLU triggers unfolded protein response not examined
    • In vivo consequences of these mutations in patient brain tissue not characterized
  10. 2016 High

    The receptor mediating microglial uptake of CLU was identified as TREM2: TREM2 directly binds CLU, Trem2 knockout microglia show impaired CLU internalization, and AD-associated TREM2 variants disrupt this interaction.

    Evidence Protein microarray screen, Co-IP, cell uptake assays in Trem2-KO primary microglia and human TREM2-variant macrophages

    PMID:27477018

    Open questions at the time
    • Whether TREM2-CLU interaction mediates Aβ clearance in vivo not demonstrated
    • Structural basis of TREM2-CLU binding not resolved
    • Contribution of other receptors (e.g., megalin/LRP2) to CLU uptake not excluded
  11. 2023 Medium

    Three studies expanded CLU's mechanistic repertoire: in cancer stem cells CLU drives AKT→DNM1L/Drp1-dependent mitophagy to sustain SOX2 stemness; SORL1 controls neuron-specific CLU levels; and the AD-risk SNP rs11136000 C allele enhances CLU expression via TDP-43 binding, leading to astrocytic interferon/CXCL10 signaling that impairs myelination.

    Evidence CLU gain/loss-of-function with phospho-Drp1 and mitophagy flux assays in oral cancer stem cells and xenografts; SORL1-null iPSC-derived neurons with proteomics and postmortem validation; CRISPR-isogenic iPSC astrocytes with allele-specific TDP-43 binding, RNA-seq, and OPC co-culture myelination assay

    PMID:36779631 PMID:37494190 PMID:37611586

    Open questions at the time
    • Whether AKT-Drp1-mitophagy axis operates outside oral cancer not tested
    • Mechanism by which SORL1 regulates CLU protein specifically in neurons unclear
    • TDP-43 binding to rs11136000 not validated in vivo
  12. 2025 High

    CLU's neuroinflammatory function was mechanistically defined: CLU deficiency in astrocytes activates NF-κB, elevates complement C3 secretion, and drives microglia-dependent synaptic loss via enhanced phagocytosis, directly linking reduced CLU to AD-related neurodegeneration.

    Evidence Unbiased proteomics in CLU-deficient astrocytes, NF-κB reporter, C3 ELISA, astrocyte-microglia co-culture synapse counting, mouse models, human plasma/brain validation

    PMID:40311610

    Open questions at the time
    • Whether CLU supplementation can rescue synaptic loss in vivo not shown
    • Specific NF-κB subunit(s) regulated by CLU not identified
    • Relative contribution of complement-dependent vs. independent microglial phagocytosis pathways not dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the three-dimensional structure of CLU, the identity of the protease that cleaves the precursor into alpha/beta chains, the full receptor repertoire for CLU uptake across cell types, and whether restoring CLU levels in astrocytes or neurons can ameliorate neurodegeneration in vivo.
  • No crystal or cryo-EM structure of CLU heterodimer
  • Processing protease identity unknown
  • Therapeutic potential of CLU modulation untested in neurodegeneration models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 1 GO:0044183 protein folding chaperone 1
Localization
GO:0005576 extracellular region 5 GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2 R-HSA-382551 Transport of small molecules 1 R-HSA-5357801 Programmed Cell Death 1 R-HSA-9612973 Autophagy 1
Partners
AKT1DNM1LHSP60SORL1TDP-43TREM2
Complex memberships
CLU-HSP60 complexHDL particleSC5b-9 (soluble membrane attack complex)

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 SP-40,40 (CLU/clusterin) is incorporated into the SC5b-9 soluble membrane attack complex of complement, functioning as an inhibitor of complement-mediated cytolysis by combining with the nascent C5b-7 complex to form a cytolytically inactive SC5b-7–SP-40,40 complex Protein purification, hemolysis inhibition assay, immunodepletion of SP-40,40 from serum followed by SC5b-9 reconstitution The Journal of clinical investigation / International immunology High 2150757 2454950 2489042
1989 The two chains (alpha and beta) of SP-40,40/CLU are encoded in a single open reading frame on the same mRNA and are generated post-synthetically by proteolytic cleavage of a biosynthetic precursor that contains a signal sequence for secretory export and six N-linked glycosylation sites cDNA cloning and sequence analysis, molecular characterization The EMBO journal High 2721499
1991 SP-40,40/CLU is associated with high-density lipoproteins (HDL) in human plasma, with up to 40–60% of NA1/NA2 (SP-40,40) co-eluting with apolipoprotein A-I-containing HDL fractions Agarose gel filtration, FPLC, anti-apoA-I immunoaffinity chromatography, partial amino acid sequencing Arteriosclerosis and thrombosis Medium 1903064
1992 All 10 cysteine residues of SP-40,40/CLU form interchain (alpha–beta) disulfide bonds arranged in an antiparallel ladder-like structure; no free sulfhydryl groups are present, and the disulfide bond motif is unique among complement proteins Tryptic peptide mapping, HPLC separation, amino acid sequencing of disulfide-containing peptides, fluorometric detection with ABD-F FEBS letters / Journal of biochemistry High 1491011 1551440
1993 Soluble amyloid-beta (Abeta) in cerebrospinal fluid is complexed with SP-40,40/CLU (apolipoprotein J) in vivo; the interaction was demonstrated by direct binding experiments with synthetic Abeta peptide and immunoprecipitation from CSF Direct binding assay with synthetic Abeta peptide, immunoprecipitation from CSF, amino acid sequencing, immunoreactivity with specific antibodies The Biochemical journal High 8328966
2015 Three patient-specific CLU mutations in the beta-chain (p.I303NfsX13, p.R338W, p.I360N) cause retention of CLU protein in the endoplasmic reticulum, reduced Golgi transport, and diminished secretion, demonstrating that the beta-chain disulfide bridge region is required for CLU heterodimerization and transit through the secretory pathway Immunocytochemistry, immunodetection, ELISA for secreted CLU, expression in HEK293T and HEK293 FLp-In cell lines Molecular neurodegeneration High 26179372
2016 TREM2 directly binds CLU/APOJ (and other apolipoproteins) as identified by unbiased protein microarray screen; TREM2 overexpression enhances CLU uptake in heterologous cells, Trem2 knockout microglia show reduced CLU internalization, and disease-associated TREM2 mutations impair this binding and uptake Protein microarray screen, Co-immunoprecipitation, cell uptake assays in heterologous cells and primary microglia, Trem2 knockout mouse microglia, human macrophages from TREM2 variant carriers Neuron High 27477018
2011 EZH2 directly represses CLU expression in neuroblastoma cells via H3K27me3 deposition at the CLU gene locus; EZH2 knockdown or pharmacological inhibition restores CLU expression, and EZH2-/- MEFs show elevated CLU mRNA RNAi knockdown of EZH2, pharmacological inhibition with 3-deazaneplanocin A, HDAC inhibitor treatment, ChIP for H3K27me3 and PRC2 components at CLU locus, comparison with EZH2-/- MEFs Cancer research High 22068036
2011 Secreted CLU (sCLU) activates AKT survival signaling, whereas intracellular CLU inhibits NF-κB transcriptional activity; intracellular CLU forms a physical complex with HSP60 in neuroblastoma cells, and HSP60 inactivates the tumor-suppressive function of intracellular CLU Immunoprecipitation (physical complex with HSP60), AKT activity assay, NF-κB reporter assay, subcellular fractionation, overexpression of secreted vs. intracellular CLU forms Cell death & disease Medium 22012253
2002 Transient CLU overexpression in SV40-immortalized human prostate epithelial cells (PNT2) causes accumulation in G0/G1, slows cell cycle progression, decreases DNA synthesis, reduces ODC and AdoMetDC activities, and increases Gas1 mRNA, demonstrating a direct anti-proliferative function Transient transfection/overexpression, flow cytometry cell cycle analysis, [3H]-thymidine incorporation, enzyme activity assays, Northern blot Oncogene Medium 12082621
2023 CLU promotes mitophagy in oral cancer stem cells by activating AKT, which phosphorylates DNM1L/Drp1 at Ser616 to initiate mitochondrial fission; CLU-mediated mitophagy degrades MSX2, preventing its nuclear translocation and thereby sustaining SOX2-dependent stemness. CLU knockdown disrupts mitochondrial metabolism and sensitizes cells to cisplatin Gain-of-function and loss-of-function (CLU overexpression and shRNA knockdown), phospho-specific western blot for DNM1L-Ser616, mitophagy flux assays, mitochondrial superoxide measurement, nuclear/cytoplasmic fractionation for MSX2, SOX2 reporter, xenograft models Autophagy Medium 36779631
2023 SORL1 loss in human iPSC-derived neurons (but not astrocytes, microglia, or endothelial cells) causes a cell-type-specific reduction in CLU protein levels; this neuron-specific SORL1–CLU relationship is validated in postmortem brain. TGF-β/SMAD signaling modulates APOE (and by implication CLU) levels in a SORL1-dependent manner SORL1-null iPSC differentiation to multiple cell types, proteomics, ELISA, retromer rescue experiments, SMAD pathway modulation, postmortem brain validation Cell reports Medium 37611586
2023 The CLU rs11136000 C risk allele is a functional variant: TDP-43 preferentially binds the C allele to promote CLU expression; C/C astrocytes show elevated interferon response and CXCL10 secretion after cytokine treatment, which inhibits oligodendrocyte progenitor cell (OPC) proliferation and myelination CRISPR-Cas9 isogenic iPSC system, allele-specific TDP-43 binding assay, RNA-seq, CXCL10 ELISA, OPC co-culture myelination assay, human brain tissue validation Cell reports High 37494190
2025 CLU deficiency in astrocytes activates NF-κB-dependent signaling and increases complement C3 secretion; reduced astrocyte CLU leads to microglia-dependent reduction of synaptic density, increased microglial phagocytosis, and altered extracellular APOE and phospho-tau levels. CLU AD-risk alleles associate with reduced CLU protein and heightened inflammatory profiles in human plasma and brain Unbiased proteomics in CLU-deficient astrocytes, functional validation (NF-κB reporter, C3 ELISA), microglia-astrocyte co-culture synapse counting, phagocytosis assay, mouse models, human plasma and brain tissue analysis Neuron High 40311610
1991 Clusterin (SGP-2) is secreted into the caput epididymal lumen, binds to spermatozoa in the caput, and then dissociates from sperm to be endocytosed by cells of the distal epididymal epithelium; testicular and epididymal forms differ in molecular weight and isoelectric point Micropuncture/microperfusion collection of luminal fluid, 2D Western blot, membrane protein extraction from spermatozoa at different epididymal regions Molecular reproduction and development Medium 1781989
1999 Extracellular CLU/SGP-2 acts as a mediator of anti-TNF-induced cytotoxicity: exogenous SGP-2 reduces TNF sensitivity in LNCaP cells, and anti-SGP-2 antibody renders TNF-resistant PC3 cells sensitive to TNF-induced cell death; this effect is reversible by adding exogenous SGP-2 Cell viability assay (trypan blue), antibody neutralization of secreted SGP-2, exogenous protein addition, Western blot of conditioned media The Prostate Medium 10221563

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nature genetics 2296 19734902
2009 Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nature genetics 2002 19734903
2016 TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia. Neuron 715 27477018
1989 Induction of the TRPM-2 gene in cells undergoing programmed death. Molecular and cellular biology 456 2477686
1988 SP-40,40, a newly identified normal human serum protein found in the SC5b-9 complex of complement and in the immune deposits in glomerulonephritis. The Journal of clinical investigation 306 2454950
1993 The cerebrospinal-fluid soluble form of Alzheimer's amyloid beta is complexed to SP-40,40 (apolipoprotein J), an inhibitor of the complement membrane-attack complex. The Biochemical journal 270 8328966
1989 Molecular cloning and characterization of the novel, human complement-associated protein, SP-40,40: a link between the complement and reproductive systems. The EMBO journal 238 2721499
2011 Genome-wide association of familial late-onset Alzheimer's disease replicates BIN1 and CLU and nominates CUGBP2 in interaction with APOE. PLoS genetics 202 21379329
2010 Replication of CLU, CR1, and PICALM associations with alzheimer disease. Archives of neurology 178 20554627
1993 Genomic organization and expression of the rat TRPM-2 (clusterin) gene, a gene implicated in apoptosis. The Journal of biological chemistry 177 7680346
1997 Intracellular levels of SGP-2 (Clusterin) correlate with tumor grade in prostate cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 158 9815554
2011 EZH2 Mediates epigenetic silencing of neuroblastoma suppressor genes CASZ1, CLU, RUNX3, and NGFR. Cancer research 153 22068036
1992 SP-40,40 is a constituent of Alzheimer's amyloid. Acta neuropathologica 147 1373021
2011 Common Alzheimer's disease risk variant within the CLU gene affects white matter microstructure in young adults. The Journal of neuroscience : the official journal of the Society for Neuroscience 145 21543606
1994 Molecular characterization of human TRPM-2/clusterin, a gene associated with sperm maturation, apoptosis and neurodegeneration. European journal of biochemistry 141 8181474
1994 Clusterin (SGP-2): a multifunctional glycoprotein with regional expression in astrocytes and neurons of the adult rat brain. The Journal of comparative neurology 138 8132868
2000 Antisense TRPM-2 oligodeoxynucleotides chemosensitize human androgen-independent PC-3 prostate cancer cells both in vitro and in vivo. Clinical cancer research : an official journal of the American Association for Cancer Research 136 10815883
2015 Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group. Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica 118 26150027
1990 Human seminal clusterin (SP-40,40). Isolation and characterization. The Journal of clinical investigation 115 2185274
1991 The SGP-2 gene is developmentally regulated in the mouse kidney and abnormally expressed in collecting duct cysts in polycystic kidney disease. Developmental biology 109 1864465
1988 Rat clusterin isolated from primary Sertoli cell-enriched culture medium is sulfated glycoprotein-2 (SGP-2). Biochemical and biophysical research communications 104 3415696
1991 Lack of correspondence between mRNA expression for a putative cell death molecule (SGP-2) and neuronal cell death in the central nervous system. Journal of neurobiology 101 1919566
2004 Clusterin (SGP-2, ApoJ) expression is downregulated in low- and high-grade human prostate cancer. International journal of cancer 88 14618611
1994 Selective expression of clusterin (SGP-2) and complement C1qB and C4 during responses to neurotoxins in vivo and in vitro. Neuroscience 83 7870303
1992 Possible functions of a new genetic marker in central nervous system: the sulfated glycoprotein-2 (SGP-2). Synapse (New York, N.Y.) 79 1626310
2016 The CLU-files: disentanglement of a mystery. Biomolecular concepts 78 26673020
1989 SP-40,40 is an inhibitor of C5b-6-initiated haemolysis. International immunology 77 2489042
2002 Clusterin (SGP-2) transient overexpression decreases proliferation rate of SV40-immortalized human prostate epithelial cells by slowing down cell cycle progression. Oncogene 74 12082621
1991 Characterization of a human high density lipoprotein-associated protein, NA1/NA2. Identity with SP-40,40, an inhibitor of complement-mediated cytolysis. Arteriosclerosis and thrombosis : a journal of vascular biology 74 1903064
2012 Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer risk. Molecular neurodegeneration 71 22248099
1998 The S. cerevisiae CLU1 and D. discoideum cluA genes are functional homologues that influence mitochondrial morphology and distribution. Journal of cell science 68 9601101
1991 SGP-2 expression as a genetic marker of progressive cellular pathology in experimental hydronephrosis. Kidney international 68 1895664
2012 Alzheimer risk variant CLU and brain function during aging. Biological psychiatry 66 22795969
1994 Gp80 (clusterin; TRPM-2) mRNA level is enhanced in human renal clear cell carcinomas. Journal of cancer research and clinical oncology 65 8263017
1999 Cytotoxic sensitivity to tumor necrosis factor-alpha in PC3 and LNCaP prostatic cancer cells is regulated by extracellular levels of SGP-2 (clusterin). The Prostate 64 10221563
1992 SP-40,40, a protein involved in the control of the complement pathway, possesses a unique array of disulphide bridges. FEBS letters 64 1551440
1990 Incorporation of SP-40,40 into the soluble membrane attack complex (SMAC, SC5b-9) of complement. International immunology 64 2150757
1991 The gene for SP-40,40, human homolog of rat sulfated glycoprotein 2, rat clusterin, and rat testosterone-repressed prostate message 2, maps to chromosome 8. Genomics 62 2045098
1996 Monitoring the temporal and spatial activation pattern of astrocytes in focal cerebral ischemia using in situ hybridization to GFAP mRNA: comparison with sgp-2 and hsp70 mRNA and the effect of glutamate receptor antagonists. Brain research 61 8911667
2012 Association of TCF4 and CLU polymorphisms with Fuchs' endothelial dystrophy and implication of CLU and TGFBI proteins in the disease process. European journal of human genetics : EJHG 60 22234156
2010 Association of CLU and PICALM variants with Alzheimer's disease. Neurobiology of aging 60 20570404
1992 Identification of the disulfide bonds in human plasma protein SP-40,40 (apolipoprotein-J). Journal of biochemistry 58 1491011
1991 Sulfated glycoprotein-2 (SGP-2) mRNA is expressed in rat striatal astrocytes following ibotenic acid lesions. Neuroscience letters 58 1749509
1990 Sandwich ELISA assay for quantitative measurement of SP-40,40 in seminal plasma and serum. Journal of immunological methods 58 2391426
1989 Localization of terminal complement components S-protein and SP-40,40 in renal biopsies. Pathology 58 2483750
2010 Genetic variations in the CLU and PICALM genes are associated with cognitive function in the oldest old. Neurobiology of aging 57 20739100
1993 Mitotic activity, apoptosis and TRPM-2 mRNA expression in DMBA-induced rat mammary carcinoma treated with anti-estrogen toremifene. International journal of cancer 57 8407000
2016 Effect of CLU genetic variants on cerebrospinal fluid and neuroimaging markers in healthy, mild cognitive impairment and Alzheimer's disease cohorts. Scientific reports 55 27229352
2001 Up-regulation of TRPM-2, MMP-7 and ID-1 during sex hormone-induced prostate carcinogenesis in the Noble rat. Carcinogenesis 54 11375906
2013 The CLU gene rs11136000 variant is significantly associated with Alzheimer's disease in Caucasian and Asian populations. Neuromolecular medicine 52 23892938
2010 Implication of CLU gene polymorphisms in Chinese patients with Alzheimer's disease. Clinica chimica acta; international journal of clinical chemistry 52 20599866
2014 Genotype patterns at CLU, CR1, PICALM and APOE, cognition and Mediterranean diet: the PREDIMED-NAVARRA trial. Genes & nutrition 51 24643340
2009 Chapter 2: Clusterin (CLU): From one gene and two transcripts to many proteins. Advances in cancer research 50 19878770
2000 Purification, characterization, and molecular cloning of acidophilic xylanase from penicillium sp.40. Bioscience, biotechnology, and biochemistry 50 10923795
2010 Genetic variability in CLU and its association with Alzheimer's disease. PloS one 49 20209083
2014 Combined effects of Alzheimer risk variants in the CLU and ApoE genes on ventricular expansion patterns in the elderly. The Journal of neuroscience : the official journal of the Society for Neuroscience 47 24806679
2015 Reduced secreted clusterin as a mechanism for Alzheimer-associated CLU mutations. Molecular neurodegeneration 46 26179372
2023 Cell-type-specific regulation of APOE and CLU levels in human neurons by the Alzheimer's disease risk gene SORL1. Cell reports 43 37611586
1995 Evidence for activation of the terminal pathway of complement and upregulation of sulfated glycoprotein (SGP)-2 in the hypoglossal nucleus following peripheral nerve injury. Molecular and chemical neuropathology 43 7755847
2009 Clusterin (CLU) and lung cancer. Advances in cancer research 42 19879423
2014 The benefits of staying active in old age: physical activity counteracts the negative influence of PICALM, BIN1, and CLU risk alleles on episodic memory functioning. Psychology and aging 40 24660791
2009 CLU and colon cancer. The dual face of CLU: from normal to malignant phenotype. Advances in cancer research 40 19879422
1995 Photoreceptor cells in the vitiligo mouse die by apoptosis. TRPM-2/clusterin expression is increased in the neural retina and in the retinal pigment epithelium. Investigative ophthalmology & visual science 38 7558712
1991 Studies on the relationship between cell proliferation and cell death: opposite patterns of SGP-2 and ornithine decarboxylase mRNA accumulation in PHA-stimulated human lymphocytes. Biochemical and biophysical research communications 38 1718280
2011 The tumour-suppressive function of CLU is explained by its localisation and interaction with HSP60. Cell death & disease 37 22012253
2017 Melittin inhibits tumor growth and decreases resistance to gemcitabine by downregulating cholesterol pathway gene CLU in pancreatic ductal adenocarcinoma. Cancer letters 36 28428074
2009 Clusterin (CLU) and prostate cancer. Advances in cancer research 35 19879420
1998 Lack of association between enhanced TRPM-2/clusterin expression and increased apoptotic activity in sex-hormone-induced prostatic dysplasia of the Noble rat. The American journal of pathology 35 9665473
1996 A ribonucleotide reductase inhibitor, MDL 101,731, induces apoptosis and elevates TRPM-2 mRNA levels in human prostate tumor xenografts. Experimental cell research 35 8549673
1996 Effects of intermittent androgen suppression on the stem cell composition and the expression of the TRPM-2 (clusterin) gene in the Shionogi carcinoma. The Journal of steroid biochemistry and molecular biology 35 9010356
2020 Lower DNA methylation levels in CpG island shores of CR1, CLU, and PICALM in the blood of Japanese Alzheimer's disease patients. PloS one 34 32991610
2015 CLU rs9331888 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Caucasian But Not East Asian Populations. Molecular neurobiology 34 25633098
1994 Increased TRPM-2/clusterin mRNA levels during the time of retinal degeneration in mouse models of retinitis pigmentosa. Biochemistry and cell biology = Biochimie et biologie cellulaire 34 7605616
2014 The ERK/eIF4F/Bcl-XL pathway mediates SGP-2 induced osteosarcoma cells apoptosis in vitro and in vivo. Cancer letters 32 25025927
2012 Implication of common and disease specific variants in CLU, CR1, and PICALM. Neurobiology of aging 32 22402018
2016 Plasma Clusterin and the CLU Gene rs11136000 Variant Are Associated with Mild Cognitive Impairment in Type 2 Diabetic Patients. Frontiers in aging neuroscience 31 27516739
1993 Regulation of Sertoli cell alpha 2-macroglobulin and clusterin (SGP-2) secretion by peritubular myoid cells. Biology of reproduction 31 7678201
1991 In vivo secretion and association of clusterin (SGP-2) in luminal fluid with spermatozoa in the rat testis and epididymis. Molecular reproduction and development 31 1781989
2014 Alzheimer's disease risk variant in CLU is associated with neural inefficiency in healthy individuals. Alzheimer's & dementia : the journal of the Alzheimer's Association 30 25496871
1996 Clusterin (SGP-2) induction in rat astroglial cells exposed to prion protein fragment 106-126. The European journal of neuroscience 30 8963451
2023 CLU (clusterin) promotes mitophagic degradation of MSX2 through an AKT-DNM1L/Drp1 axis to maintain SOX2-mediated stemness in oral cancer stem cells. Autophagy 29 36779631
1993 SP-40,40 immunoreactivity in inflammatory CNS lesions displaying astrocyte/oligodendrocyte interactions. Journal of neuropathology and experimental neurology 29 8440994
2022 The role and function of CLU in cancer biology and therapy. Clinical and experimental medicine 27 36098834
2018 Liposomal co-delivery-based quantitative evaluation of chemosensitivity enhancement in breast cancer stem cells by knockdown of GRP78/CLU. Journal of liposome research 27 29262741
2025 CLU alleviates Alzheimer's disease-relevant processes by modulating astrocyte reactivity and microglia-dependent synaptic density. Neuron 26 40311610
2013 CLU genetic variants and cognitive decline among elderly and oldest old. PloS one 26 24244428
1997 TRPM-2 expression and tunel staining in neurodegenerative diseases: studies in wobbler and rd mice. Experimental neurology 26 9056387
2011 CLU, CR1 and PICALM genes associate with Alzheimer's-related senile plaques. Alzheimer's research & therapy 25 21466683
2009 CLU "in and out": looking for a link. Advances in cancer research 25 19879425
2023 Astrocytic response mediated by the CLU risk allele inhibits OPC proliferation and myelination in a human iPSC model. Cell reports 24 37494190
1997 The effects of spinal cord injury on the status of messenger ribonucleic acid for TRPM 2 and androgen receptor in the prostate of the rat. Journal of andrology 24 9203052
1991 Assignment of a human serum glycoprotein SP-40,40 gene (CLI) to chromosome 8. Cytogenetics and cell genetics 24 1660393
2014 SGP-2, an acidic polysaccharide from Sarcandra glabra, inhibits proliferation and migration of human osteosarcoma cells. Food & function 23 24336744
2013 Expression of Clu and Tgfb1 during murine tooth development: effects of in-vivo transfection with anti-miR-214. European journal of oral sciences 23 23841781
2013 Age-dependent effect of Alzheimer's risk variant of CLU on EEG alpha rhythm in non-demented adults. Frontiers in aging neuroscience 23 24379779
2009 Chapter 5: Nuclear CLU (nCLU) and the fate of the cell. Advances in cancer research 23 19878773
1997 Effect of heat shock treatment on the production of variant testosterone-repressed prostate message-2 (TRPM-2) mRNA in culture cells. Cell biochemistry and function 23 9415971
2018 Association between CLU gene rs11136000 polymorphism and Alzheimer's disease: an updated meta-analysis. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 22 29396813
2009 The role of clusterin (CLU) in malignant transformation and drug resistance in breast carcinomas. Advances in cancer research 22 19879421
2000 Increased levels of clusterin (SGP-2) mRNA and protein accompany rat ventral prostate involution following finasteride treatment. The Journal of endocrinology 21 11054633