Clusterin is a protein found throughout the body, involved in numerous biological processes. Its widespread presence hints at its diverse roles, making it a subject of ongoing scientific investigation. It is involved in various physiological functions and associated with different health conditions.
Understanding Clusterin
Clusterin, also known as apolipoprotein J (ApoJ), is a glycoprotein present in almost all mammalian tissues and bodily fluids, including plasma, urine, and cerebrospinal fluid. This protein exists in various forms within cells, including secreted, cytoplasmic, and nuclear types, with its relative molecular weight varying due to differences in glycosylation and cleavage. The secreted form (sCLU) is highly glycosylated, accounting for about 30% of its total mass, and is typically found in blood and cerebrospinal fluid, usually existing as dimers or tetramers due to hydrophobic regions.
Clusterin’s Diverse Functions
Clusterin acts as an extracellular molecular chaperone, meaning it helps prevent misfolded proteins from clumping together in bodily fluids. It binds to these non-native proteins, maintaining them in a soluble state until they can be properly refolded by other chaperones or degraded. This chaperone activity is important for preventing stress-induced aggregation of blood plasma proteins.
The protein also plays a role in regulating programmed cell death, known as apoptosis. Clusterin can protect cells against apoptosis by reducing the activity of pro-apoptotic proteins such as BCL2 associated X apoptosis regulator (BAX). Its involvement extends to facilitating the clearance of apoptotic cells by macrophages, a process that helps prevent inflammation and autoimmune responses.
Clusterin is involved in lipid transport, associating with lipids and potentially contributing to cholesterol recycling processes in the brain. Clusterin modulates immune responses, interacting with components of the complement system and potentially influencing antigen presentation. It also participates in cell adhesion and tissue remodeling, affecting how cells interact with each other and their surrounding environment.
Clusterin’s Role in Disease
Clusterin is implicated in neurodegenerative diseases, particularly Alzheimer’s disease (AD). It is a genetic factor associated with an increased risk of late-onset AD, and its relationship with amyloid-beta (Aβ) plaques is a key research area. Clusterin influences Aβ aggregation and clearance, and some studies suggest it may mediate Aβ toxicity.
In cancer, clusterin often exhibits complex and sometimes contradictory roles. While it can promote tumor cell survival and resistance to therapy, its expression can also be protective. Its involvement in cancer progression includes cell proliferation, apoptosis, metastasis, and drug resistance.
Clusterin is also associated with kidney diseases, specifically diabetic kidney disease (DKD). Research indicates that clusterin levels are linked to renal dysfunction and can serve as a biomarker for renal tubular injury. Upregulation of clusterin in diseased kidneys may represent a self-protective response, aiming to alleviate kidney damage.
In cardiovascular diseases, clusterin’s function appears to be protective for cardiac cells during damage. Its expression often increases in the heart after injury, and its protective capacity is attributed to its anti-apoptotic and anti-oxidant properties. Clusterin’s presence has also been noted in atherosclerotic plaques.