Clusterin (secreted form) (CLU)

Secreted clusterin (sCLU), also known as Apolipoprotein J or CLU, is a highly glycosylated, heterodimeric protein secreted into plasma and body fluids, where it acts as an extracellular molecular chaperone[1][2][3][5][6][8]. Clusterin stabilizes misfolded proteins, prevents their aggregation, and mediates their clearance by cellular uptake, contributing to tissue homeostasis and cellular stress protection[1][2][3][5][6][8]. sCLU collects at sites of tissue stress, inflammation, and injury, and is upregulated in multiple disease states, including cancer, neurodegenerative diseases (notably Alzheimer’s disease), cardiovascular and fibrotic disorders[2][3][4][5][6][7]. Functionally, sCLU can promote cell survival via inhibition of proapoptotic proteins, modulation of signaling pathways such as ERK1/2 and PI3K/AKT, and regulation of immune and inflammatory responses[1][3][4][5][6]. High expression of clusterin in tumors is associated with poor prognosis and increased chemoresistance; its inhibition has been clinically tested as a strategy to sensitize cancer cells to chemotherapy[4]. Conversely, in neurodegenerative disease, increased CLU provides neuroprotection by binding toxic amyloid beta peptides and reducing their aggregation and toxicity, and also supports synaptic health[2][3][5][7]. Clusterin has become a widely studied biomarker of disease progression in Alzheimer’s disease, certain cancers, and cardiovascular/metabolic disorders[2][3][4][5][6][7].

Other names

Secreted clusterinsCLUApolipoprotein JCLITRPM-2

Antisense inhibition (e.g., OGX-011 reduces CLU synthesis to sensitize cancer cells to chemotherapy); CLU helps prevent apoptosis and promotes cell survival, making cells more resistant to chemotherapeutics such as cisplatin; Tumor cell proliferation and chemoresistance via ERK1/2 signaling; CLU inhibition disrupts this pathway; Epigenetic regulation (HDAC inhibitors increase CLU expression as a protective mechanism)