Affinage

CLU

Clusterin · UniProt P10909

Length
449 aa
Mass
52.5 kDa
Annotated
2026-06-09
100 papers in source corpus 26 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLU (clusterin/APOJ/SP-40,40/SGP-2) is a secreted, disulfide-linked heterodimeric glycoprotein that functions broadly in extracellular protein homeostasis, complement regulation, lipid transport, and cell-survival signaling (PMID:2454950, PMID:2721499). The mature protein is generated from a single precursor by proteolytic cleavage into alpha and beta chains that carry a signal sequence and six N-linked glycosylation sites, with all ten cysteines engaged in a unique antiparallel inter-chain disulfide ladder rather than free thiols (PMID:2721499, PMID:1491011, PMID:1551440). As a constituent of the terminal complement pathway, secreted CLU is incorporated stoichiometrically into the soluble SC5b-9 complex and inhibits complement-mediated hemolysis by capturing the nascent C5b-7 intermediate to form a cytolytically inactive complex (PMID:2454950, PMID:2489042, PMID:2150757). CLU additionally circulates as an HDL-associated apolipoprotein bound to apoA-I particles (PMID:1903064) and forms specific complexes with soluble amyloid-beta in cerebrospinal fluid, where it is also a component of Alzheimer amyloid deposits (PMID:8328966, PMID:1373021). In the brain, CLU is internalized by microglia through direct binding to the receptor TREM2, and disease-associated TREM2 mutations impair this uptake (PMID:27477018); astrocytic CLU restrains NF-kappaB-dependent complement C3 secretion to govern astrocyte-microglia crosstalk and synaptic integrity (PMID:40311610). Coding mutations in the CLU beta chain found in Alzheimer patients disrupt heterodimerization and cause ER retention with reduced secretion (PMID:26179372), while the rs11136000 C risk allele enhances TDP-43 binding to drive CLU overexpression, elevated CXCL10, and impaired oligodendrocyte progenitor myelination (PMID:37494190). In cancer, CLU expression is epigenetically silenced by EZH2-deposited H3K27me3 (PMID:22068036); secreted CLU activates pro-survival AKT signaling and confers chemoresistance and protection from TNF-induced apoptosis, whereas intracellular CLU inhibits NF-kappaB and is itself sequestered by HSP60 (PMID:10815883, PMID:22012253, PMID:10221563). CLU also acts as an anti-proliferative regulator that arrests cells in G0/G1 (PMID:12082621) and, at mitochondria, serves as a mitophagy adaptor bridging BAX and LC3 while activating AKT-driven DNM1L phosphorylation to couple mitochondrial quality control to cancer stemness (PMID:36779631, PMID:38447939).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1988 High

    Establishing what CLU does began with identifying it as a physical component of the soluble complement membrane attack complex, defining its first molecular role.

    Evidence Protein isolation and reconstitution of purified SP-40,40 into the SC5b-9 complex with complement hemolysis assays

    PMID:2454950

    Open questions at the time
    • Did not define the mechanism of complement inhibition
    • Did not establish binding stoichiometry or partner subunit
  2. 1988 High

    Cross-species protein sequencing resolved that the secreted complement protein and rat Sertoli-cell sulfated glycoprotein-2 are the same molecule, unifying disparate research lines onto one gene.

    Evidence HPLC purification, N-terminal sequencing of both subunits, and cDNA cloning from a testicular library

    PMID:3415696

    Open questions at the time
    • Did not address functional conservation between tissues
    • Did not define the secretion pathway
  3. 1989 High

    Defining how complement inhibition works showed CLU intercepts the nascent C5b-7 intermediate to form an inactive complex, more potently than vitronectin.

    Evidence Dose-dependent purified-protein hemolysis inhibition and co-complex formation assays

    PMID:2489042

    Open questions at the time
    • Did not map the C5b-7 binding interface on CLU
    • Did not establish in vivo physiological relevance
  4. 1989 High

    Molecular cloning explained the biosynthetic architecture, revealing a single secreted precursor proteolytically cleaved into two glycosylated chains.

    Evidence cDNA cloning, ORF and sequence analysis identifying signal sequence and N-glycosylation sites

    PMID:2721499

    Open questions at the time
    • Did not identify the processing protease
    • Did not define the inter-chain linkage
  5. 1992 High

    Disulfide mapping resolved the structural basis of heterodimerization, showing all ten cysteines form a unique antiparallel inter-chain ladder with no free thiols.

    Evidence Tryptic peptide mapping, RP-HPLC, fluorometric thiol detection, and disulfide peptide sequencing

    PMID:1491011 PMID:1551440

    Open questions at the time
    • Did not relate disulfide architecture to functional activity at the time
    • No high-resolution structure of the assembled dimer
  6. 1991 High

    Biochemical fractionation extended CLU function beyond complement by showing it circulates as an HDL-associated apolipoprotein on apoA-I particles.

    Evidence Agarose gel filtration, FPLC, anti-apoA-I immunoaffinity chromatography, and immunoblotting

    PMID:1903064

    Open questions at the time
    • Did not define the lipid-binding region
    • Did not establish a role in lipid metabolism
  7. 1993 High

    Demonstrating a direct CLU-amyloid-beta complex in CSF connected the protein to Alzheimer pathology mechanistically.

    Evidence Direct binding, immunoprecipitation of soluble Abeta from CSF, sequencing, and amyloid deposit immunohistochemistry

    PMID:1373021 PMID:8328966

    Open questions at the time
    • Did not determine whether CLU promotes or clears amyloid
    • Did not identify a clearance receptor
  8. 2000 High

    Loss-of-function in prostate cancer established CLU overexpression as a driver of chemoresistance, defining a therapeutic rationale.

    Evidence Antisense ODN knockdown with chemotherapy combination, apoptosis readouts (PARP cleavage, DNA laddering), and xenograft validation

    PMID:10815883

    Open questions at the time
    • Did not distinguish secreted versus intracellular CLU contributions
    • Did not define the survival signaling pathway
  9. 2002 Medium

    Gain-of-function defined an intrinsic anti-proliferative, cell-cycle-regulatory role for CLU, complicating its purely pro-survival image.

    Evidence Transient overexpression in prostate epithelial cells with flow cytometry, BrdU incorporation, enzyme activity assays, and Gas1 expression

    PMID:12082621

    Open questions at the time
    • Transient overexpression may not reflect physiological isoform balance
    • Did not reconcile anti-proliferative versus pro-survival roles mechanistically
  10. 2011 Medium

    Isoform-specific analysis separated CLU's opposing activities: secreted CLU activates AKT survival signaling while intracellular CLU inhibits NF-kappaB and is neutralized by HSP60.

    Evidence Secreted versus intracellular construct overexpression, AKT phosphorylation and NF-kappaB activity assays, and HSP60 co-immunoprecipitation

    PMID:22012253

    Open questions at the time
    • Single lab without reciprocal validation of HSP60 interaction
    • Did not define how HSP60 binding inactivates CLU
  11. 2011 High

    ChIP-based analysis identified the upstream epigenetic control of CLU, showing EZH2 directly silences the locus via H3K27me3.

    Evidence EZH2 RNAi and pharmacological inhibition, ChIP for H3K27me3/PRC2 at the CLU locus, and EZH2-knockout MEFs

    PMID:22068036

    Open questions at the time
    • Did not establish what de-represses CLU in disease
    • Did not link epigenetic state to specific CLU isoform output
  12. 2016 High

    Identifying TREM2 as a direct CLU-binding receptor explained how microglia internalize CLU and connected it to genetic Alzheimer risk.

    Evidence Unbiased protein microarray, binding assays with disease variants, TREM2-overexpression and knockout uptake assays, and human variant macrophages

    PMID:27477018

    Open questions at the time
    • Did not determine the fate of internalized CLU-Abeta cargo
    • Did not map the CLU-TREM2 binding interface
  13. 2015 High

    Patient-derived mutations linked CLU secretory trafficking to Alzheimer disease, showing beta-chain mutations cause ER retention and reduced secretion.

    Evidence Mutant construct expression in HEK cells with immunocytochemistry, Western blot, and ELISA for secreted CLU

    PMID:26179372

    Open questions at the time
    • Did not establish that reduced secretion causes disease in vivo
    • Limited to overexpression systems
  14. 2023 Medium

    iPSC modeling placed SORL1 and TGF-beta/SMAD signaling upstream of neuronal CLU expression, defining a regulatory axis.

    Evidence SORL1-null iPSC differentiation, proteomics, retromer rescue, SMAD modulation, and postmortem brain validation

    PMID:37611586

    Open questions at the time
    • TGF-beta/SMAD link inferred from modulation rather than direct binding
    • Single lab
  15. 2023 High

    An isogenic CRISPR system converted the rs11136000 GWAS association into a functional mechanism, showing the C allele enhances TDP-43 binding to raise CLU and impair myelination.

    Evidence CRISPR isogenic iPSC astrocytes, TDP-43 allele-specific binding, CXCL10 measurement, OPC proliferation/myelination assays, and human brain analysis

    PMID:37494190

    Open questions at the time
    • Did not reconcile CLU overexpression risk with secretion-loss mutations
    • Mechanism of CXCL10-driven OPC inhibition not fully resolved
  16. 2023 Medium

    Cancer-cell studies revealed an unexpected mitochondrial role for CLU as a mitophagy adaptor coupling quality control to stemness.

    Evidence CLU gain/loss-of-function, co-IP with BAX and LC3, mitochondrial fractionation, AKT/DNM1L phosphorylation, and MSX2/SOX2 assays

    PMID:36779631

    Open questions at the time
    • Full adaptor mechanism not reconstituted in vitro
    • Single lab
  17. 2024 Medium

    Follow-up work extended the mitochondrial model, coupling CLU-driven mitophagy to PGC1alpha-dependent biogenesis and cytoprotection.

    Evidence CLU overexpression/knockdown, mitochondrial imaging, co-IP, mitochondrial PI3K activity assay, PPARGC1A siRNA/inhibitor, and xenografts

    PMID:38447939

    Open questions at the time
    • How a secreted glycoprotein accesses the mitochondrial matrix remains unresolved
    • Single lab
  18. 2025 High

    Astrocyte-specific loss-of-function defined CLU as a regulator of glial crosstalk and synaptic integrity through suppression of NF-kappaB/C3 signaling.

    Evidence CLU-deficient astrocytes, unbiased proteomics, C3/phagocytosis/synapse-density readouts, and validation in human AD risk-allele tissue

    PMID:40311610

    Open questions at the time
    • Did not define the receptor mediating astrocyte CLU's NF-kappaB suppression
    • Did not reconcile protective astrocyte CLU with pathogenic overexpression

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how CLU's opposing roles — secreted pro-survival versus intracellular tumor-suppressive, protective versus pathogenic in the brain, extracellular chaperone versus mitochondrial adaptor — are coordinated by isoform identity, trafficking, and disease context.
  • No unifying model reconciles secretion-loss and overexpression risk alleles
  • Mechanism routing CLU to mitochondria is undefined
  • Receptors mediating intracellular signaling effects largely unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2 GO:0008289 lipid binding 1
Localization
GO:0005576 extracellular region 3 GO:0005739 mitochondrion 2 GO:0005634 nucleus 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2 R-HSA-162582 Signal Transduction 1
Partners
APOA1BAXC5B-7HSP60MAP1LC3TARDBPTREM2
Complex memberships
SC5b-9 soluble membrane attack complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 SP-40,40 (CLU/APOJ) was identified as a component of the SC5b-9 soluble membrane attack complex of complement, and purified SP-40,40 was incorporated into this complex in vitro, establishing CLU as a constituent of the terminal complement pathway regulator. Protein isolation, immunological characterization, complement hemolysis assay, incorporation into SC5b-9 complex The Journal of clinical investigation High 2454950
1989 SP-40,40 (CLU) inhibits complement-mediated hemolysis by combining with nascent C5b-7 complex to form a cytolytically inactive SC5b-7-SP-40,40 complex, functioning analogously to but more potently than S-protein (vitronectin) on an equimolar basis. Purified protein hemolysis inhibition assay (dose-dependent), co-complex formation assessment International immunology High 2489042
1990 SP-40,40 (CLU) is incorporated into SC5b-9 as one molecule per complex alongside S-protein; either SP-40,40 or S-protein alone is sufficient to form soluble C5b-9 complex, demonstrated by depletion of each from serum using affinity chromatography. Affinity column depletion of SP-40,40 or S-protein from serum, inulin activation, SDS-PAGE densitometry International immunology High 2150757
1989 The CLU gene encodes a single precursor protein whose two chains (alpha and beta) are generated by post-translational proteolytic cleavage, with the precursor containing a signal sequence for secretion and six N-linked glycosylation sites distributed equally between the two chains. cDNA cloning, sequence analysis, open reading frame analysis The EMBO journal High 2721499
1992 All 10 cysteine residues in SP-40,40 (CLU) are involved in inter-chain (alpha-beta) disulfide bonds with no free cysteines, forming a unique antiparallel ladder-like disulfide bond structure between the two chains. Tryptic digestion, reversed-phase HPLC peptide mapping, fluorometric detection with ABD-F, amino acid sequencing of disulfide-containing peptides Journal of biochemistry High 1491011 1551440
1993 Soluble amyloid-beta (Aβ) in cerebrospinal fluid forms a specific complex with SP-40,40/ApoJ (CLU) in vivo, as demonstrated by immunoprecipitation of soluble Aβ from CSF using anti-SP-40,40 antibodies, and CLU is found as a constituent of Alzheimer's amyloid deposits. Direct binding experiments, immunoprecipitation from cerebrospinal fluid, amino acid sequencing, immunoreactivity with specific antibodies The Biochemical journal High 1373021 8328966
1991 CLU (SP-40,40/NA1-NA2) is physically associated with high-density lipoproteins (HDL), with up to 60% of CLU co-eluting with HDL fractions and at least 40% associated with apoA-I-containing particles, establishing CLU as an HDL-associated apolipoprotein. Agarose gel filtration, FPLC, anti-apoA-I immunoaffinity chromatography, immunoblotting, partial amino acid sequencing Arteriosclerosis and thrombosis High 1903064
1990 Human seminal CLU (clusterin/SP-40,40) demonstrates hemagglutination (cell clustering) activity and inhibition of C5b-6-initiated hemolysis comparable to serum-derived CLU, despite charge differences on 2D gels, confirming both activities are intrinsic to the protein. Protein purification, 2D gel electrophoresis, hemagglutination assay, C5b-6 hemolysis inhibition assay The Journal of clinical investigation Medium 2185274
1988 Rat clusterin isolated from Sertoli cell cultures was identified as identical to sulfated glycoprotein-2 (SGP-2) by N-terminal amino acid sequence analysis of both the alpha (43 kDa) and beta (35 kDa) subunits and cDNA cloning from a testicular library. Protein purification by HPLC, N-terminal amino acid sequencing, cDNA library screening with anti-alpha subunit antibody Biochemical and biophysical research communications High 3415696
2000 Antisense oligodeoxynucleotides (ODNs) targeting the TRPM-2/CLU translation initiation site significantly suppress CLU expression in PC-3 prostate cancer cells and, in combination with paclitaxel or mitoxantrone, enhance chemosensitivity and apoptosis (PARP cleavage, DNA laddering) both in vitro and in vivo, establishing CLU overexpression as a mechanism of chemoresistance. Antisense ODN knockdown, Western blot, in vitro cell viability, in vivo xenograft tumor volume, TUNEL staining, DNA laddering, PARP cleavage Clinical cancer research High 10815883
1991 CLU (clusterin/SGP-2) is secreted into the caput epididymal lumen in vivo and binds to spermatozoa in the caput epididymis, then dissociates from sperm for endocytosis by distal epididymal epithelial cells, establishing a specific spatial pattern of CLU-sperm association during maturation. Micropuncture/microperfusion of seminiferous tubule and epididymal fluids, 2D Western blot, membrane extract analysis Molecular reproduction and development Medium 1781989
2011 Secreted CLU activates the survival kinase AKT, while intracellular CLU inhibits NF-κB activity; furthermore, intracellular CLU forms a physical complex with HSP60, which inactivates intracellular CLU's tumor-suppressive function in neuroblastoma cells. Overexpression of secreted vs. intracellular CLU isoforms, AKT phosphorylation assay, NF-κB activity assay, co-immunoprecipitation with HSP60 Cell death & disease Medium 22012253
2011 EZH2 directly represses CLU expression in neuroblastoma cells via H3K27me3 deposition at the CLU gene locus; EZH2 knockdown or pharmacological inhibition increases CLU expression, and EZH2−/− MEFs show elevated CLU mRNA, establishing EZH2 as an epigenetic writer that silences CLU. RNA interference knockdown of EZH2, pharmacological inhibition with 3-deazaneplanocin A, ChIP for H3K27me3 and PRC2 components at CLU locus, EZH2 knockout MEF comparison, HDAC inhibitor treatment Cancer research High 22068036
2016 TREM2 binds directly to CLU/APOJ (and APOE) on an unbiased protein microarray, and TREM2 overexpression enhances cellular uptake of CLU while TREM2 knockout in microglia reduces CLU internalization; disease-associated TREM2 mutations impair CLU binding and uptake. Protein microarray screen, binding assays with disease-variant mutants, overexpression uptake assays in heterologous cells, Trem2 knockout microglia uptake assay, macrophages from human TREM2 variant carriers Neuron High 27477018
2015 Three CLU β-chain mutations found in AD patients (p.I303NfsX13, p.R338W, p.I360N) alter CLU subcellular localization, causing CLU to accumulate in the ER rather than the Golgi, reduce CLU transport through the secretory pathway, and diminish CLU secretion; the mechanism for two missense mutations involves disruption of the disulfide bridge region affecting heterodimerization. Immunocytochemistry, immunodetection (Western blot), ELISA for secreted CLU, expression of mutant constructs in HEK293T and HEK293 FLp-In cells Molecular neurodegeneration High 26179372
2023 SORL1 loss in human iPSC-derived neurons specifically reduces CLU protein levels in a neuron-cell-type-specific manner, linked to TGF-β/SMAD signaling; modulating SMAD signaling alters CLU (and APOE) RNA levels in a SORL1-dependent fashion, placing SORL1 upstream of CLU regulation via this pathway. SORL1-null iPSC differentiation to multiple cell types, proteomics, retromer-mediated trafficking rescue, SMAD signaling modulation, postmortem brain validation Cell reports Medium 37611586
2025 Loss of CLU in astrocytes increases NF-κB-dependent signaling and complement C3 secretion; reduced astrocyte CLU induces microglia-dependent extracellular APOE and phosphorylated tau modulation, increased microglial phagocytosis, and reduced synapse numbers, establishing CLU as a regulator of astrocyte–microglia crosstalk and synaptic integrity. CLU-deficient astrocytes, unbiased proteomic profiling, functional validation in mouse and human cellular models, plasma and brain tissue analysis from AD risk allele carriers Neuron High 40311610
2023 CLU rs11136000 is identified as a functional SNP: the C allele promotes TDP-43 binding to the CLU locus, increasing CLU expression; C/C astrocytes show elevated interferon response and CXCL10 expression upon cytokine stimulation, which inhibits oligodendrocyte progenitor cell (OPC) proliferation and myelination. CRISPR-Cas9 isogenic iPSC-derived astrocytes (C vs. T allele), small-scale CRISPR screen, TDP-43 binding assay, CXCL10 measurement, OPC proliferation and myelination assay, human brain tissue analysis Cell reports High 37494190
2023 CLU promotes mitophagy in oral cancer stem cells by localizing to mitochondria and acting as an adaptor protein that interacts with BAX and LC3 to recruit autophagic machinery around damaged mitochondria; CLU also activates AKT to phosphorylate DNM1L/Drp1 at Ser616, initiating mitochondrial fission. CLU-mediated mitophagy causes degradation of MSX2, preventing its nuclear translocation and thereby maintaining SOX2-dependent cancer stemness. CLU gain- and loss-of-function, co-immunoprecipitation of CLU with BAX and LC3, mitochondrial fractionation, AKT/DNM1L phosphorylation assays, MSX2 nuclear translocation assays, SOX2 activity assays, cisplatin treatment models Autophagy Medium 36779631
2024 CLU localizes to mitochondria in oral cancer cells and coordinates mitophagy by acting as an adaptor recruiting LC3 to damaged mitochondria, activating class III PI3K activity at mitochondria; in parallel, CLU-induced mitophagy is coupled to PPARGC1A/PGC1α-dependent mitochondrial biogenesis, and inhibition of PPARGC1A counteracts CLU-dependent cytoprotection leading to mitophagy-associated cell death. CLU overexpression/knockdown, mitochondrial localization imaging, co-immunoprecipitation with BAX and LC3, PI3K activity assay at mitochondria, siRNA against PPARGC1A, pharmacological inhibitor SR-18292, xenograft tumor model Autophagy Medium 38447939
1993 Peritubular myoid cells modulate Sertoli cell secretion of clusterin (SGP-2): direct co-culture experiments showed that peritubular myoid cells alter the amounts of clusterin secreted by Sertoli cells, while FSH, testosterone, and IL-6 had no effect on clusterin secretion, but dexamethasone stimulated it dose-dependently. Primary Sertoli cell cultures with and without peritubular myoid cells, immunoassay for secreted proteins, dose-response with FSH, testosterone, IL-6, dexamethasone Biology of reproduction Medium 7678201
2002 Transient overexpression of clusterin in SV40-immortalized human prostate epithelial cells (PNT2) causes increased accumulation in G0/G1 phases, slowdown of cell cycle progression, decreased DNA synthesis, decreased ODC and AdoMetDC activities, and increased Gas1 mRNA (marker of quiescence), establishing a direct anti-proliferative, cell-cycle-regulatory function for CLU. Transient transfection overexpression, cell cycle analysis by flow cytometry, BrdU incorporation, ODC and AdoMetDC enzymatic activity assays, Northern blot for Gas1 and histone H3 mRNA Oncogene Medium 12082621
1999 Extracellular CLU (SGP-2) protects PC-3 prostate cancer cells from TNF-alpha-induced cytotoxicity: PC-3 cells (high CLU secretors) are resistant to TNF, and anti-CLU antibody renders them sensitive; conversely, addition of exogenous CLU to LNCaP cells (low CLU) reduces their TNF sensitivity, establishing secreted CLU as an extracellular anti-apoptotic mediator against TNF. Exogenous CLU addition, anti-CLU antibody neutralization, Western blot of conditioned media, cell viability by trypan blue exclusion The Prostate Medium 10221563
1997 CLU protein shows anomalous nuclear localization in androgen-independent Shionogi carcinoma cells (in addition to cytoplasmic staining), with more intense nuclear staining in recurrent androgen-independent cells, suggesting that nuclear CLU may inhibit early apoptotic events and promote survival of androgen-independent stem cells. Immunohistochemistry with anti-clusterin antibody on tumor sections across cycles of androgen withdrawal, in vivo limiting dilution assay for stem cells The Journal of steroid biochemistry and molecular biology Low 9010356

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia. Neuron 730 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 307 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
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 137 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 120 26150027
1990 Human seminal clusterin (SP-40,40). Isolation and characterization. The Journal of clinical investigation 116 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 72 22248099
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
2010 Association of CLU and PICALM variants with Alzheimer's disease. Neurobiology of aging 61 20570404
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
1990 Sandwich ELISA assay for quantitative measurement of SP-40,40 in seminal plasma and serum. Journal of immunological methods 59 2391426
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
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 56 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
2010 Genetic variability in CLU and its association with Alzheimer's disease. PloS one 50 20209083
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
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 49 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 45 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
2011 The tumour-suppressive function of CLU is explained by its localisation and interaction with HSP60. Cell death & disease 38 22012253
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
2017 Melittin inhibits tumor growth and decreases resistance to gemcitabine by downregulating cholesterol pathway gene CLU in pancreatic ductal adenocarcinoma. Cancer letters 36 28428074
1996 A ribonucleotide reductase inhibitor, MDL 101,731, induces apoptosis and elevates TRPM-2 mRNA levels in human prostate tumor xenografts. Experimental cell research 36 8549673
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 35 32991610
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 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
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
2012 Implication of common and disease specific variants in CLU, CR1, and PICALM. Neurobiology of aging 33 22402018
2025 CLU alleviates Alzheimer's disease-relevant processes by modulating astrocyte reactivity and microglia-dependent synaptic density. Neuron 32 40311610
2014 The ERK/eIF4F/Bcl-XL pathway mediates SGP-2 induced osteosarcoma cells apoptosis in vitro and in vivo. Cancer letters 32 25025927
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
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 30 36779631
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
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 28 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
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
2023 Astrocytic response mediated by the CLU risk allele inhibits OPC proliferation and myelination in a human iPSC model. Cell reports 25 37494190
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
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
2024 CLU (clusterin) and PPARGC1A/PGC1α coordinately control mitophagy and mitochondrial biogenesis for oral cancer cell survival. Autophagy 21 38447939
2000 Increased levels of clusterin (SGP-2) mRNA and protein accompany rat ventral prostate involution following finasteride treatment. The Journal of endocrinology 21 11054633
1994 Gene relaxation and aging: changes in the abundance of rat ventral prostate SGP-2 (clusterin) and ornithine decarboxylase mRNAs. FEBS letters 21 8034050
2021 The expression of FLNA and CLU in PBMCs as a novel screening marker for hepatocellular carcinoma. Scientific reports 20 34290294
2020 Exploring the Role of CLU in the Pathogenesis of Alzheimer's Disease. Neurotoxicity research 20 32820456

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