Clusterin Human
Description
Molecular Structure and Isoforms
Clusterin exists as a disulfide-linked heterodimer (α-Clu and β-Clu chains) in its secreted form (sCLU), with a molecular weight of 75–80 kDa . Key structural features include:
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α-Clu: Contains five β-propeller domains, critical for protein interactions .
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β-Clu: Exhibits lipid-binding domains, influencing cellular lipid metabolism .
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N-glycosylation: Variable glycosylation patterns affect its apparent molecular weight and subcellular localization .
Table 2: Tissue-Specific Expression of Clusterin
Pathological Roles and Disease Associations
Clusterin is implicated in neurodegeneration, cancer, and metabolic disorders:
Alzheimer’s Disease (AD)
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Biomarker: Elevated in AD cerebrospinal fluid (CSF) and associated with Aβ plaques .
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Dual Role:
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Genetic Risk: CLU rs11136000 variant increases AD risk by 16–18% .
Cancer
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Pro-Survival: Overexpression in prostate, breast, and lung cancers correlates with chemoresistance .
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Mechanisms: Activates AKT/PI3K and ERK pathways, inhibits p53-mediated apoptosis .
Traumatic Brain Injury (TBI)
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Biomarker: Plasma clusterin levels decrease acutely post-TBI but rise chronically, correlating with brain injury severity .
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Localization: Extracellular punctate staining in perilesional cortex and thalamus .
Table 3: Clusterin in Disease Pathogenesis
Isoform-Specific Functions
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mitoCLU: Protects against TDP-43 and tau aggregation in neurodegenerative models .
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nCLU: Silencing enhances Aβ-induced neurotoxicity, suggesting therapeutic potential .
Targeting Clusterin in AD
Product Specs
Product Science Overview
Clusterin, also known as Apolipoprotein J, Sulfated Glycoprotein 2 (SGP-2), TRPM-2, and SP-40,40, is a secreted multifunctional protein that was named for its ability to induce cellular clustering . It is a glycoprotein with multiple biological functions and is involved in various physiological and pathological processes within the organism . Clusterin is predominantly expressed in adult testis, ovary, adrenal gland, liver, heart, and brain, and in many epithelial tissues during embryonic development .
Clusterin is synthesized as a precursor that contains two coiled coil domains, three nuclear localization signals (NLS), and one heparin binding domain . It binds a wide range of molecules and may function as a chaperone of misfolded extracellular proteins . The protein is involved in processes such as regulating inflammation, controlling cell apoptosis, and clearing pathological proteins .
Clusterin has attracted extensive research attention, particularly in Alzheimer’s disease (AD) research. It plays a significant role in the disease’s occurrence and progression. The expression level of Clusterin in the brain tissue of AD patients is closely related to pathological progression. Clusterin is involved in the deposition and formation of β-amyloid, which is a crucial process in AD development . Furthermore, Clusterin may affect the pathogenesis of AD through mechanisms such as regulating inflammation, controlling cell apoptosis, and clearing pathological proteins .
Recombinant human Clusterin is produced using advanced biotechnological methods. It is typically derived from a mouse myeloma cell line, NS0, and is expressed as a disulfide-linked heterodimer . The recombinant protein is purified to a high degree, with a purity greater than 90% as determined by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining . The endotoxin level is kept below 1.0 EU per 1 μg of the protein by the LAL method .
