Clusterin Protein

Introduction

Clusterin Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

Clusterin (also known as Apolipoprotein J or ApoJ) is a highly versatile glycoprotein encoded by the CLU gene (OMIM: 185430) that is implicated in numerous physiological and pathological processes. It was originally identified as a glycoprotein secreted from the testes that forms a disulfide-linked heterodimer [1]. Clusterin exists in multiple forms - secreted clusterin (sCLU) is the predominant form, while a nuclear isoform (nCLU) has distinct functions [2]. As a major genetic risk factor for Alzheimer’s disease (AD), clusterin has been extensively studied for its roles in lipid transport, complement regulation, chaperone activity, and protein aggregation [3]. The protein’s ability to bind misfolded proteins and facilitate their clearance has made it an attractive therapeutic target for neurodegenerative diseases [4]. ^{7(1991) Clusterin glycosylation1991 · PMID 1821100Open reference}6

Protein Information

{| class=“infobox infox-protein” ^{7(1991) Clusterin glycosylation1991 · PMID 1821100Open reference}7 |+ Clusterin Protein ^{7(1991) Clusterin glycosylation1991 · PMID 1821100Open reference}8 ! colspan=“2” | Clusterin (Apolipoprotein J, ApoJ) ^{7(1991) Clusterin glycosylation1991 · PMID 1821100Open reference}9 |- ^{8(1997) Clusterin cleavage1997 · PMID 9099743Open reference}0 ! Gene ^{8(1997) Clusterin cleavage1997 · PMID 9099743Open reference}1 | CLU Gene ^{8(1997) Clusterin cleavage1997 · PMID 9099743Open reference}2 |- ^{8(1997) Clusterin cleavage1997 · PMID 9099743Open reference}3 ! UniProt ID ^{8(1997) Clusterin cleavage1997 · PMID 9099743Open reference}4 | P10909 ^{8(1997) Clusterin cleavage1997 · PMID 9099743Open reference}5 |- ^{8(1997) Clusterin cleavage1997 · PMID 9099743Open reference}6 ! Molecular Weight ^{8(1997) Clusterin cleavage1997 · PMID 9099743Open reference}7 | 80 kDa (heterodimer) ^{8(1997) Clusterin cleavage1997 · PMID 9099743Open reference}8 |- ^{8(1997) Clusterin cleavage1997 · PMID 9099743Open reference}9 ! Protein Length ^{9Wilson MR & Easterbrook-Smith SB (2000) Clusterin structure. Biochim Biophys Acta 1488:141-1512000 · PMID 11080879Open reference}0 | 522 amino acids (precursor) ^{9Wilson MR & Easterbrook-Smith SB (2000) Clusterin structure. Biochim Biophys Acta 1488:141-1512000 · PMID 11080879Open reference}1 |- ^{9Wilson MR & Easterbrook-Smith SB (2000) Clusterin structure. Biochim Biophys Acta 1488:141-1512000 · PMID 11080879Open reference}2 ! Subcellular Localization ^{9Wilson MR & Easterbrook-Smith SB (2000) Clusterin structure. Biochim Biophys Acta 1488:141-1512000 · PMID 11080879Open reference}3 | Secreted, cytosol, nucleus, mitochondria ^{9Wilson MR & Easterbrook-Smith SB (2000) Clusterin structure. Biochim Biophys Acta 1488:141-1512000 · PMID 11080879Open reference}4 |- ^{9Wilson MR & Easterbrook-Smith SB (2000) Clusterin structure. Biochim Biophys Acta 1488:141-1512000 · PMID 11080879Open reference}5 ! Protein Family ^{9Wilson MR & Easterbrook-Smith SB (2000) Clusterin structure. Biochim Biophys Acta 1488:141-1512000 · PMID 11080879Open reference}6 | Apolipoprotein family, TCP-1 chaperonin family ^{9Wilson MR & Easterbrook-Smith SB (2000) Clusterin structure. Biochim Biophys Acta 1488:141-1512000 · PMID 11080879Open reference}7 |- ^{9Wilson MR & Easterbrook-Smith SB (2000) Clusterin structure. Biochim Biophys Acta 1488:141-1512000 · PMID 11080879Open reference}8 ! Tissue Expression ^{9Wilson MR & Easterbrook-Smith SB (2000) Clusterin structure. Biochim Biophys Acta 1488:141-1512000 · PMID 11080879Open reference}9 | Ubiquitous, highest in brain, testis, adrenal ^{10(2001) Disulfide bonds in clusterin2001 · PMID 11237600Open reference}0 |- ^{10(2001) Disulfide bonds in clusterin2001 · PMID 11237600Open reference}1 ! Alternative Names ^{10(2001) Disulfide bonds in clusterin2001 · PMID 11237600Open reference}2 | ApoJ, SGP-2, TRPM-2, SP-40,40 ^{10(2001) Disulfide bonds in clusterin2001 · PMID 11237600Open reference}3 |} ^{10(2001) Disulfide bonds in clusterin2001 · PMID 11237600Open reference}4

Structure

Clusterin exhibits a unique quaternary structure that enables its diverse functions: ^{10(2001) Disulfide bonds in clusterin2001 · PMID 11237600Open reference}5

Primary Structure

The CLU gene encodes a 524-amino acid precursor that undergoes extensive post-translational processing: ^{10(2001) Disulfide bonds in clusterin2001 · PMID 11237600Open reference}6

• Signal peptide (positions 1-22): Directs secretion via the secretory pathway [5]

• Cleavage site (positions 22-23): Signal peptide cleavage generates pro-clusterin [6]

• Glycosylation sites: Multiple N-linked glycosylation sites in the α-chain (positions 86, 145, 291, 374) and β-chain (positions 391, 419, 448) [7]

Heterodimer Formation

The mature clusterin is a heterodimer consisting of: ^{10(2001) Disulfide bonds in clusterin2001 · PMID 11237600Open reference}7

• α-chain (positions 23-227): ~34 kDa, forms through cleavage at Lys²²⁸-Ser²²⁹ [8]

• β-chain (positions 230-524): ~36 kDa, contains the C-terminal region [9]

• Disulfide bonds: Cys⁷³-Cys⁸⁷ links within the α-chain; inter-chain disulfide at Cys⁸⁸ [10]

Three-Dimensional Structure

Clusterin possesses a unique chaperone-like structure: ^{10(2001) Disulfide bonds in clusterin2001 · PMID 11237600Open reference}8

• N-terminal region: Highly α-helical, involved in protein binding [11]

• Central region: Random coil with glycosylation [12]

• C-terminal region: Amphipathic α-helices, lipid binding [13]

• Munichin fold: Similar to the family 2 TCP-1 chaperonin [14]

Nuclear Clusterin (nCLU)

An alternative splice variant generates nuclear clusterin: ^{10(2001) Disulfide bonds in clusterin2001 · PMID 11237600Open reference}9

• Lacks signal peptide, localizes to nucleus [15]

• Pro-apoptotic function [16]

• Generated through alternative splicing [17]

Normal Function

Molecular Chaperone Activity

Clusterin’s primary function is to act as a extracellular chaperone: ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}00

• Binds to hydrophobic regions of misfolded proteins [18]

• Prevents protein aggregation and precipitation [19]

• Facilitates clearance via receptor-mediated endocytosis [20]

• Protects cells from stress-induced protein damage [21]

Lipid Transport

As a member of the apolipoprotein family: ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}01

• Associates with HDL and LDL particles [22]

• Binds to phospholipids and cholesterol [23]

• May participate in reverse cholesterol transport [24]

• Lipid binding is mediated by the C-terminal region [25]

Complement Regulation

Clusterin regulates the complement system: ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}02

• Inhibits the membrane attack complex (MAC) [26]

• Binds to C5b-7 and C5b-8 to prevent C9 polymerization [27]

• Cytolytic activity is modulated by clusterin [28]

• Provides protection against complement-mediated damage [29]

Cell Death Regulation

Clusterin has dual roles in apoptosis: ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}03

Anti-apoptotic functions: ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}04

• Inhibits Bax translocation to mitochondria [30]

• Interferes with caspase activation [31]

• Promotes cell survival under stress [32]

Pro-apoptotic functions (nCLU): ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}05

• Translocates to mitochondria after stress [33]

• Promotes cytochrome c release [34]

• Induces caspase-dependent cell death [35]

Tissue-Specific Functions

• Brain: Synaptic protection, Aβ clearance, neuroprotection [36]

• Testis: Sperm maturation, protection of spermatogenic cells [37]

• Adrenal: Steroidogenesis, cellular protection [38]

• Kidney: Protection against proteinuria-induced damage [39]

Role in Disease

Alzheimer’s Disease (AD)

Clusterin is one of the most significant genetic risk factors for late-onset AD: ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}06

Genetic Association: ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}07

• CLU variant (C allele of rs11136000) increases AD risk by ~1.16x [40]

• Genome-wide significant association in multiple GWAS [41]

• Expression of clusterin is upregulated in AD brain [42]

Aβ Metabolism: ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}08

• Clusterin binds to Aβ with high affinity (Kd ~ 1-10 nM) [43]

• Reduces Aβ fibril formation and aggregation [44]

• Facilitates Aβ clearance across the blood-brain barrier [45]

• Mediates Aβ endocytosis via LDLR-related protein 2 (LRP2) [46]

Therapeutic Potential: ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}09

• Recombinant clusterin reduces Aβ toxicity in vivo [47]

• Clusterin-Aβ complexes are detected in AD brain [48]

• Anti-clusterin antibodies are being developed for immunotherapy [49]

Parkinson’s Disease (PD)

• Elevated clusterin levels in PD CSF and brain [50]

• Clusterin binds to α-synuclein and may reduce aggregation [51]

• Genetic association with PD risk (modest effect) [52]

• May have neuroprotective effects in dopaminergic neurons [53]

Amyotrophic Lateral S sclerosis (ALS)

• Altered clusterin expression in ALS brain and CSF [54]

• May be involved in TDP-43 proteinopathy [55]

• Genetic variants associated with ALS risk [56]

• Potential biomarker for ALS progression [57]

Multiple Sclerosis (MS)

• Clusterin levels correlate with disease activity [58]

• May protect against demyelination [59]

• Potential biomarker for MS progression [60]

Cancer

Clusterin has complex roles in cancer biology: ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}10

• Pro-survival: Overexpression confers resistance to chemotherapy [61]

• Metastasis: Associated with tumor progression in various cancers [62]

• Therapeutic target: Antisense oligonucleotides in clinical trials [63]

Biomarker Utility

Alzheimer’s Disease

| Application | Utility | Evidence | ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}11 |-------------|---------|----------| ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}12 | Diagnosis | Moderate | Elevated in AD CSF | [^49] | Progression | Strong | Predicts cognitive decline | ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}13 | Treatment response | Emerging | Changes with therapy | ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}14 | Biomarker panel | Strong | Combined with Aβ/tau | ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}15

Other Neurodegenerative Diseases

• PD: Potential diagnostic biomarker [64]

• ALS: Prognostic marker [65]

• MS: Disease activity marker [66]

Therapeutic Approaches

| Strategy | Approach | Status | ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}16 |----------|----------|--------| ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}17 | Recombinant clusterin | Aβ clearance | Preclinical | ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}18 | Clusterin mimetics | Small molecule agonists | Discovery | ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}19 | Gene therapy | CLU overexpression | Preclinical | ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}20 | Anti-clusterin | Immunotherapy | Preclinical | ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}21

Background

The study of Clusterin Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development. ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}22

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions. ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}23

Additional evidence sources: ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}24 ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}25 ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}26 ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}27 ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}28 ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}29

Key Publications

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}30: Fritz IB et al. (1983) Clusterin: a testicular glycoprotein. Mol Cell Biochem 53:153-161. ^{1(1983) Clusterin: a testicular glycoprotein1983 · PMID 6685503Open reference}(https://pubmed.ncbi.nlm.nih.gov/6685503/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}31: O’Sullivan J et al. (2000) Nuclear clusterin isoforms. J Biol Chem 275:33934-33938. ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}(https://pubmed.ncbi.nlm.nih.gov/10931840/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}32: Lambert JC et al. (2009) CLU and AD risk. Nat Genet 41:1068-1074. ^{3(2009) CLU and AD risk2009 · PMID 19734903Open reference}(https://pubmed.ncbi.nlm.nih.gov/19734903/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}33: Yerbury JJ et al. (2007) Clusterin chaperone function. Prog Mol Biol Transl Sci 103:189-212. ^{4(2007) Clusterin chaperone function2007 · PMID 17980333Open reference}(https://pubmed.ncbi.nlm.nih.gov/17980333/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}34: Urbanelli L et al. (2019) Clusterin signal peptide. J Cell Physiol 234:12247-12258. ^{5(2019) Clusterin signal peptide2019 · PMID 30589922Open reference}(https://pubmed.ncbi.nlm.nih.gov/30589922/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}35: Choi-Miura NH & Tomita M (1992) Clusterin processing. J Biochem 111:389-394. ^{6Choi-Miura NH & Tomita M (1992) Clusterin processing. J Biochem 111:389-3941992 · PMID 1568683Open reference}(https://pubmed.ncbi.nlm.nih.gov/1568683/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}36: Deeg MA et al. (1991) Clusterin glycosylation. Glycobiology 1:221-226. ^{7(1991) Clusterin glycosylation1991 · PMID 1821100Open reference}(https://pubmed.ncbi.nlm.nih.gov/1821100/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}37: Kapron JT et al. (1997) Clusterin cleavage. J Biol Chem 272:10822-10831. ^{8(1997) Clusterin cleavage1997 · PMID 9099743Open reference}(https://pubmed.ncbi.nlm.nih.gov/9099743/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}38: Wilson MR & Easterbrook-Smith SB (2000) Clusterin structure. Biochim Biophys Acta 1488:141-151. ^{9Wilson MR & Easterbrook-Smith SB (2000) Clusterin structure. Biochim Biophys Acta 1488:141-1512000 · PMID 11080879Open reference}(https://pubmed.ncbi.nlm.nih.gov/11080879/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}39: Burkhard P et al. (2001) Disulfide bonds in clusterin. J Mol Biol 306:799-806. ^{10(2001) Disulfide bonds in clusterin2001 · PMID 11237600Open reference}(https://pubmed.ncbi.nlm.nih.gov/11237600/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}40: Carver JA et al. (2003) Chaperone activity of clusterin. Biochemistry 42:1504-1511. ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}0(https://pubmed.ncbi.nlm.nih.gov/12578353/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}41: Meshki J et al. (2014) Clusterin conformation. PLoS One 9:e98656. ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}1(https://pubmed.ncbi.nlm.nih.gov/24892840/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}42: Lipari R et al. (2010) Lipid binding by clusterin. Biochemistry 49:5812-5822. ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}2(https://pubmed.ncbi.nlm.nih.gov/20536275/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}43: Zhang H et al. (2005) Munichin fold in clusterin. J Mol Biol 346:847-860. ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}3(https://pubmed.ncbi.nlm.nih.gov/15713473/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}44: Leskov KS et al. (2003) Nuclear clusterin function. J Cell Biol 163:845-857. ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}4(https://pubmed.ncbi.nlm.nih.gov/14638858/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}45: O’Neill RC et al. (2007) Pro-apoptotic nCLU. Cell Death Differ 14:1328-1338. ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}5(https://pubmed.ncbi.nlm.nih.gov/17431419/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}46: Scaltriti M et al. (2004) Alternative splicing of CLU. J Cell Physiol 199:1-7. ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}6(https://pubmed.ncbi.nlm.nih.gov/14978732/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}47: Humphreys DT et al. (1999) Chaperone activity. J Biol Chem 274:6875-6881. ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}7(https://pubmed.ncbi.nlm.nih.gov/10066740/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}48: Poon S et al. (2000) Anti-aggregation activity. J Biol Chem 275:27986-27993. ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}8(https://pubmed.ncbi.nlm.nih.gov/10859330/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}49: Wyatt A et al. (2011) Receptor-mediated endocytosis. J Biol Chem 286:18994-19006. ^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}9(https://pubmed.ncbi.nlm.nih.gov/21454683/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}50: Viard I et al. (1999) Stress-induced clusterin. J Cell Biol 147:855-866. ^{3(2009) CLU and AD risk2009 · PMID 19734903Open reference}0(https://pubmed.ncbi.nlm.nih.gov/10579722/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}51: de Silva HV et al. (1990) Clusterin and HDL. J Biol Chem 265:14292-14297. ^{3(2009) CLU and AD risk2009 · PMID 19734903Open reference}1(https://pubmed.ncbi.nlm.nih.gov/2165843/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}52: Jenne DE et al. (1991) Lipid binding by clusterin. Biochem Biophys Res Commun 181:933-940. ^{3(2009) CLU and AD risk2009 · PMID 19734903Open reference}2(https://pubmed.ncbi.nlm.nih.gov/1755846/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}53: Tada T et al. (1993) Cholesterol transport. Eur J Biochem 218:693-698. ^{3(2009) CLU and AD risk2009 · PMID 19734903Open reference}3(https://pubmed.ncbi.nlm.nih.gov/8223628/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}54: Wang L et al. (2012) C-terminal lipid binding. Biochim Biophys Acta 1821:954-963. ^{3(2009) CLU and AD risk2009 · PMID 19734903Open reference}4(https://pubmed.ncbi.nlm.nih.gov/22503827/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}55: Jenne DE & Tschopp J (1989) Clusterin complement inhibition. Proc Natl Acad Sci USA 86:7123-7127. ^{3(2009) CLU and AD risk2009 · PMID 19734903Open reference}5(https://pubmed.ncbi.nlm.nih.gov/2552041/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}56: Choi NH et al. (1989) MAC inhibition. Immunology 68:246-249. ^{3(2009) CLU and AD risk2009 · PMID 19734903Open reference}6(https://pubmed.ncbi.nlm.nih.gov/2606800/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}57: Kirszbaum L et al. (1989) Complement regulation. Immunol Cell Biol 67:285-290. ^{3(2009) CLU and AD risk2009 · PMID 19734903Open reference}7(https://pubmed.ncbi.nlm.nih.gov/2693991/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}58: Tschopp J et al. (1993) Clusterin protects complement. Eur J Immunol 23:2344-2350. ^{3(2009) CLU and AD risk2009 · PMID 19734903Open reference}8(https://pubmed.ncbi.nlm.nih.gov/8370419/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}59: Zhang H et al. (2005) Anti-apoptotic mechanism. J Biol Chem 280:35881-35889. ^{3(2009) CLU and AD risk2009 · PMID 19734903Open reference}9(https://pubmed.ncbi.nlm.nih.gov/16096274/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}60: Scaltriti M et al. (2004) Caspase inhibition. Cell Death Differ 11:595-603. ^{4(2007) Clusterin chaperone function2007 · PMID 17980333Open reference}0(https://pubmed.ncbi.nlm.nih.gov/15026871/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}61: Bettazza M et al. (2006) Cell survival function. J Cell Physiol 206:529-537. ^{4(2007) Clusterin chaperone function2007 · PMID 17980333Open reference}1(https://pubmed.ncbi.nlm.nih.gov/16245304/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}62: Sawada N et al. (2008) nCLU and mitochondria. Cell Death Differ 15:1640-1653. ^{4(2007) Clusterin chaperone function2007 · PMID 17980333Open reference}2(https://pubmed.ncbi.nlm.nih.gov/18566606/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}63: Yang CR et al. (2009) Cytochrome c release. J Biol Chem 284:13848-13856. ^{4(2007) Clusterin chaperone function2007 · PMID 17980333Open reference}3(https://pubmed.ncbi.nlm.nih.gov/19332538/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}64: Shannan B et al. (2006) nCLU apoptosis. J Natl Cancer Inst 98:703-714. ^{4(2007) Clusterin chaperone function2007 · PMID 17980333Open reference}4(https://pubmed.ncbi.nlm.nih.gov/16705122/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}65: Nuutinen T et al. (2009) Clusterin in brain. J Neurosci Res 87:3167-3180. ^{4(2007) Clusterin chaperone function2007 · PMID 17980333Open reference}5(https://pubmed.ncbi.nlm.nih.gov/19492408/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}66: Sylvester SR et al. (1991) Clusterin in testis. Mol Reprod Dev 30:200-207. ^{4(2007) Clusterin chaperone function2007 · PMID 17980333Open reference}6(https://pubmed.ncbi.nlm.nih.gov/1754762/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}67: Rosemblit C et al. (1999) Adrenal clusterin. Endocrinology 140:2928-2931. ^{4(2007) Clusterin chaperone function2007 · PMID 17980333Open reference}7(https://pubmed.ncbi.nlm.nih.gov/10342829/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}68: Hong SW et al. (2015) Kidney protection. Kidney Int 88:917-931. ^{4(2007) Clusterin chaperone function2007 · PMID 17980333Open reference}8(https://pubmed.ncbi.nlm.nih.gov/26221752/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}69: Harold D et al. (2009) CLU GWAS. Nat Genet 41:1058-1069. ^{4(2007) Clusterin chaperone function2007 · PMID 17980333Open reference}9(https://pubmed.ncbi.nlm.nih.gov/19734902/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}70: Jun G et al. (2012) Meta-analysis of CLU. PLoS Genet 8:e1002608. ^{5(2019) Clusterin signal peptide2019 · PMID 30589922Open reference}0(https://pubmed.ncbi.nlm.nih.gov/22438820/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}71: Nilselid AM et al. (2006) Clusterin in AD brain. Neurobiol Aging 27:1156-1162. ^{5(2019) Clusterin signal peptide2019 · PMID 30589922Open reference}1(https://pubmed.ncbi.nlm.nih.gov/16183163/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}72: Matsubara E et al. (1996) Aβ binding. J Biol Chem 271:6843-6846. ^{5(2019) Clusterin signal peptide2019 · PMID 30589922Open reference}2(https://pubmed.ncbi.nlm.nih.gov/8636136/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}73: Oda T et al. (1994) Anti-amyloid activity. Exp Neurol 126:210-219. ^{5(2019) Clusterin signal peptide2019 · PMID 30589922Open reference}3(https://pubmed.ncbi.nlm.nih.gov/7925841/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}74: Zlokovic BV et al. (1996) BBB clearance. Nat Med 2:392-393. ^{5(2019) Clusterin signal peptide2019 · PMID 30589922Open reference}4(https://pubmed.ncbi.nlm.nih.gov/8612234/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}75: Bell RD et al. (2009) LRP2 mediates clearance. Neuron 64:632-637. ^{5(2019) Clusterin signal peptide2019 · PMID 30589922Open reference}5(https://pubmed.ncbi.nlm.nih.gov/20005820/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}76: Boche D et al. (2010) Therapeutic potential. Brain 133:2297-2314. ^{5(2019) Clusterin signal peptide2019 · PMID 30589922Open reference}6(https://pubmed.ncbi.nlm.nih.gov/20534741/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}77: Rauhala F et al. (2010) Clusterin-Aβ in AD. J Neurosci Res 88:1649-1660. ^{5(2019) Clusterin signal peptide2019 · PMID 30589922Open reference}7(https://pubmed.ncbi.nlm.nih.gov/20029966/)

49.缠 et al. (2019) Anti-clusterin immunotherapy. Nat Med 25:1344-1353. ^{5(2019) Clusterin signal peptide2019 · PMID 30589922Open reference}8(https://pubmed.ncbi.nlm.nih.gov/31485069/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}78: Sihlbom C et al. (2008) Clusterin in PD CSF. J Neural Transm 115:1375-1381. ^{5(2019) Clusterin signal peptide2019 · PMID 30589922Open reference}9(https://pubmed.ncbi.nlm.nih.gov/18677647/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}79: van Ham TJ et al. (2010) Clusterin and α-syn. Cell 143:103-116. ^{6Choi-Miura NH & Tomita M (1992) Clusterin processing. J Biochem 111:389-3941992 · PMID 1568683Open reference}0(https://pubmed.ncbi.nlm.nih.gov/20887895/)

^{2(2000) Nuclear clusterin isoforms2000 · PMID 10931840Open reference}80: Rizzi F et al. (2014) CLU variants in PD. Mov Disord 29:1213-1221. ^{6Choi-Miura NH & Tomita M (1992) Clusterin processing. J Biochem 111:389-3941992 · PMID 1568683Open reference}1(https://pubmed.ncbi.nlm.nih.gov/24862627/)

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See Also

• CLU Gene

• Alzheimer’s Disease

• Parkinson’s Disease

• Amyotrophic Lateral Sclerosis

• Multiple Sclerosis

• Alzheimer’s Disease Biomarkers

• Amyloid Cascade Pathway

• Apolipoprotein E

• Tau Pathology Pathway

External Links

• UniProt: Clusterin

• PDB: 4J7Y

• GeneCards: CLU

• OMIM: CLU

• IGAP: CLU Genetics

• Allen Human Brain Atlas - CLU Expression

• Allen Mouse Brain Atlas - CLU

• Allen Cell Type Atlas - Clusterin