Clu

Fig1. Clusterin synthesis and functions inside the cell. (Carmen Rodríguez-Rivera, 2021)

What is CLU Protein?

CLU, or clusterin, is a protein that humans produce from the CLU gene located on chromosome 8. It's like a helper protein that hangs out in the body fluids and works to neutralize harmful proteins that aren't folded correctly. Think of it as a crisis manager, dragging these troublemakers into cells where they're broken down and disposed of. It gets involved in a bunch of conditions like neurodegenerative diseases, certain cancers, and even things related to aging. It's got this structure that lets it float around outside cells, making sure everything's running smoothly. Overall, clusterin's got a pretty big role in keeping cells healthy and functioning as they should.

What is the Function of CLU Protein?

Clusterin, also known as CLU, is quite the versatile protein floating around in human fluids. Think of it as a clean-up crew that deals with misfolded proteins, stopping them from causing trouble by binding to them and helping cells gobble them up for recycling. It's like a guardian angel in many chronic conditions – you'll find it playing roles in brain diseases like Alzheimer's and inflammation-related issues. It's also got a hand in cancer scenarios, sometimes helping tumors survive by dodging cell death, which makes it a target for some clever therapy strategies. All in all, CLU is a busybody in regulating processes that keep cells healthy or lead them down the path of disease.

CLU Related Signaling Pathway

The CLU protein, known as clusterin or apolipoprotein J, acts as a molecular chaperone that keeps proteins from misfolding in the body and guides damaged ones to be broken down. It plays roles in a plethora of conditions like neurodegenerative diseases and cancer. Clusterin is heavily involved in the process of endocytosis, where cells take in substances, and its presence is seen across various tissues and body fluids. In diseases such as Alzheimer's, clusterin levels in the bloodstream have shown some correlation with how fast the disease progresses. Beyond just being a protector against cellular stress, it also intertwines with various signaling pathways, sometimes helping cells survive hostile conditions like chemotherapy by meddling with pathways related to cell death and survival mechanisms. So, it's quite a multifunctional player in our biological systems.

CLU Related Diseases

Clusterin, often known by other names like apolipoprotein J, plays a significant role in various diseases. It's linked with neurodegenerative conditions like Alzheimer's, where higher blood levels of clusterin seem to coincide with faster cognitive decline, though it's not clear if it sparks the disease onset. In cancer, clusterin's got this quirky dual role; it can either help tumors resist treatments, particularly in cancers like prostate and ovarian, or it becomes sparse, which makes cells more vulnerable to therapy as seen in testicular cancer. On top of that, clusterin is up to its old tricks in cardiovascular diseases and conditions related to oxidative stress like aging. It even assists the Hepatitis C virus by stabilizing elements critical for the virus's life cycle. With its involvement in such diverse processes, scientists see it as a potential target for therapies aimed at cancer, neurodegenerative diseases, and viral infections.

Bioapplications of CLU

Clusterin, often abbreviated as CLU, is a protein with notable versatility, acting as a chaperone to prevent protein aggregation. It's been extensively studied in research and industrial circles for its protective role against cellular stress and involvement in various diseases such as cancer and neurodegenerative disorders. In scientific investigations, CLU is utilized to explore mechanisms of cell protection, apoptosis, and protein stabilization. Furthermore, due to its influence on tumor microenvironments and response to therapies, CLU is examined as a potential target for enhancing cancer treatment efficacy. Its regulatory role in lipid metabolism and cell death pathways also makes it valuable in developing therapeutic approaches for metabolic and degenerative diseases, showcasing its significant applications across research-driven fields.

Case Study 1: Ivo Doudevski, 2014

This study dives into why clusterin pairs up with exfoliation deposits in glaucoma patients. Researchers checked out lens deposits using atomic force microscopy and confocal immunofluorescence. They spotted a dense fibrillar web on the side of the lens facing the aqueous humor, but the opposite side didn't show anything notable. Clusterin was snugly integrated with these fibrils. Additionally, glaucoma patients with these deposits had higher levels of certain complement components and inhibitors in their eye fluid, suggesting a link to inflammation. This highlights a possible pathogenic mechanism involving the immune system's complement pathway in exfoliation glaucoma.

Fig1. Illustrates the specificity of H330 anti-clusterin antibody.

Fig2. Atomic-force microscopy image of anterior lens capsules prior and subsequent to clusterin immunolabeling.

Case Study 2: So Young Gil, 2013

Researchers have been digging deep into the brain's feeding circuits to maintain energy balance, trying to find out how different biological molecules fit into the picture. They've discovered that when they give mice a dose of clusterin, also known as apolipoprotein J, it makes the mice eat less, lose weight, and activates a signaling pathway in the hypothalamus. Conversely, if clusterin's action in the hypothalamus is blocked, the mice end up eating more and gaining weight, which isn't so great because it leads to fat accumulation. This process seems to hinge on the interaction between the low-density lipoprotein receptor-related protein-2, a potential partner for clusterin, and the long-form leptin receptor. In response to clusterin, the connection between these two proteins gets way stronger in cultured brain cells, and if there's a glitch with the leptin receptor or the low-density protein receptor gets suppressed, clusterin signaling goes off track. This research points out a new pathway in the hypothalamus where clusterin plays a big role in appetite suppression, closely linked with leptin receptor signaling.

Fig3. Effects of ICV infusion of an anticlusterin neutralizing antibody.

Fig4. The effects of starvation on clusterin protein levels in the hypothalamus (H), plasma (P) and CSF (C) in satiated Sprague–Dawley rats.

Clu has several biochemical functions, for example, NOT ATPase activity,chaperone binding,misfolded protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by Clu itself. We selected most functions Clu had, and list some proteins which have the same functions with Clu. You can find most of the proteins on our site.

Clu has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with Clu here. Most of them are supplied by our site. Hope this information will be useful for your research of Clu.

PDIA3;ADCYAP1;FOS;PPARG;Stag2;NR3C1;ZNF24;NR4A1;MDM2;BCL2L1;KLF11;POLR1C;CYP2E1