The Influence of Clusterin Glycosylation Variability on Selected Pathophysiological Processes in the Human Body

Abstract

The present review gathers together the most important information about variability in clusterin molecular structure, its profile, and the degree of glycosylation occurring in human tissues and body fluids in the context of the utility of these characteristics as potential diagnostic biomarkers of selected pathophysiological conditions. The carbohydrate part of clusterin plays a crucial role in many biological processes such as endocytosis and apoptosis. Many pathologies associated with neurodegeneration, carcinogenesis, metabolic diseases, and civilizational diseases (e.g., cardiovascular incidents and male infertility) have been described as causes of homeostasis disturbance, in which the glycan part of clusterin plays a very important role. The results of the discussed studies suggest that glycoproteomic analysis of clusterin may help differentiate the severity of hippocampal atrophy, detect the causes of infertility with an immune background, and monitor the development of cancer. Understanding the mechanism of clusterin (CLU) action and its binding epitopes may enable to indicate new therapeutic goals. The carbohydrate part of clusterin is considered necessary to maintain its proper molecular conformation, structural stability, and proper systemic and/or local biological activity. Taking into account the wide spectrum of CLU action and its participation in many processes in the human body, further studies on clusterin glycosylation variability are needed to better understand the molecular mechanisms of many pathophysiological conditions. They can also provide the opportunity to find new biomarkers and enrich the panel of diagnostic parameters for diseases that still pose a challenge for modern medicine.

Maximizing Glycoproteomics Results through an Integrated Parallel Accumulation Serial Fragmentation Workflow

“…Conventional shotgun proteomics CID energies typically yield predominant glycan fragmentation with insufficient peptide fragment ions to confidently identify the glycopeptide. 36 To address this limitation, we systematically adjusted collision energies to enhance the yield of the peptide backbone fragments in our approach.…”

“…The identification of glycopeptides by tandem mass spectrometry poses a significant challenge due to the need for optimal fragmentation of both the peptide moiety and the intrinsically different glycan moiety. Conventional shotgun proteomics CID energies typically yield predominant glycan fragmentation with insufficient peptide fragment ions to confidently identify the glycopeptide . To address this limitation, we systematically adjusted collision energies to enhance the yield of the peptide backbone fragments in our approach.…”

Alzheimer's Disease Investigated via Gene-Environment Interactions, Biochemical Pathways, Cellular Processes, and Disease Phenotype Variability

“…Furthermore, CLU has been implicated in the regulation of tau phosphorylation, a key event in the development of neuro brillary tangles (NFTs) in Alzheimer's disease. It may modulate microtubule stability and dynamics, in uencing the aggregation and accumulation of hyperphosphorylated tau protein [75,77]. Moreover, CLU is involved in lipid metabolism, including cholesterol transport and metabolism in the brain.…”

Milk Fat Globules: 2024 Updates

“…161 Clusterin and lactadherin also play a role in cell damage and apoptosis, and consequently, in gut epithelial homeostasis. 162 Hormone-sensitive lipase, peroxisomal bifunctional enzyme, peroxisomal multifunctional enzyme type 2, peroxisomal acyl-coenzyme A oxidase 3, carboxyl ester lipase (GD3, BSSL), and sphingomyelin phosphodiesterase promote lipid digestion. 16 Ribonucleic acid (RNA) in the MFG membrane: The cytoplasmic crescent of the MFG membrane holds cellular and microRNAs (miRNAs).…”