Clusterin (CLU)

Clusterin (CLU), a predominantly secreted glycoprotein, is composed of two chains: α-clusterin (α-Clu) and β-clusterin (β-Clu), and they are linked by disulfide bonds. CLU is expressed in a variety of tissues and is present in the extracellular space and several body fluids. There are different proteoforms of CLU, and mutations in the protein might cause its altered localization and functions in the cell. After discovered as a cell-aggregating factor found in ram testis fluid, many roles have been ascribed to clusterin, including lipid transport, regulation, complement inhibition, cell differentiation, regulation of inflammation, appetite, apoptosis, as well as protein quality control in the extracellular space. Besides, CLU has been displayed to display chaperone-like activity and exhibit the chemically-induced and heat-induced amorphous aggregation.

Until now, the exact role of CLU in several conditions is indistinct, however, it is associated with neurodegenerative disorders such as several cancers, Alzheimer’s, chronic inflammatory disorders, and autoimmune disorders. Importantly, CLU has been identified as a biomarker of Alzheimer’s disease in a range of genome-wide association studies. In addition, CLU was demonstrated to modulate the activity of leptin and act as an anorexigenic molecule in animals. It has also been proven to bind to promoter regions of Sterol Regulatory Element Binding Protein-1C (SREBP-1C), which is a master regulator of several lipid metabolic pathways and controlling its expression and suppressing hepatic lipid accumulation.

Fig.1 Role of clusterin in the brain vascular clearance of amyloid-β. (Nelson, 2017)

Reference

1. Nelson, A. R., et al. Role of clusterin in the brain vascular clearance of amyloid-β. Proceedings of the National Academy of Sciences. 2017,114(33), 8681-8682.