Clusterin (CLU) (CLU)

Clusterin (CLU), also known as Apolipoprotein J, is a highly conserved, multifunctional glycoprotein that acts primarily as an extracellular chaperone (UniProt P10909). It is synthesized as a precursor polypeptide that undergoes proteolytic cleavage and subsequent disulfide bonding to form a mature secreted heterodimer consisting of an alpha and a beta chain (Rohne et al., 2016, PMID: 26912498). The secreted clusterin (sCLU) isoform plays a critical role in proteostasis by binding to misfolded proteins and facilitating their clearance, thereby preventing protein aggregation (Jones & Jomary, 2002, PMID: 11955499). In oncology, sCLU is recognized as a potent anti-apoptotic factor that is upregulated in response to cellular stress, such as chemotherapy or radiation, leading to treatment resistance in various malignancies including prostate and lung cancer (Zoubeidi & Gleave, 2012, PMID: 22564338). Therapeutic efforts have targeted the clusterin mRNA using antisense oligonucleotides like Custirsen (OGX-011) to inhibit the production of both chains, aiming to enhance the efficacy of standard cancer therapies (Chi et al., 2017, PMID: 28221864). Additionally, clusterin is a major genetic risk factor for late-onset Alzheimer's disease, where it is thought to influence amyloid-beta clearance and neuroinflammation (Foster et al., 2019, PMID: 31133913).

Other names

Apolipoprotein JAPOJComplement-associated protein SP-40,40Complement cytolysis inhibitorCLISulfated glycoprotein 2SGP-2Testosterone-repressed prostate message 2TRPM-2Secreted clusterin beta chain

Antisense oligonucleotide-mediated inhibition of clusterin mRNA translation, which prevents the synthesis of the clusterin precursor protein and its subsequent cleavage into alpha and beta chains.