Cystatin C, also known as Cystatin-3 (CST3) is a secreted type 2 cysteine protease inhibitor synthesized in all nucleated cells, has been proposed as a replacement for serum creatinine for the assessment of renal function, particularly to detect small reductions in glomerular filtration rate. Cystatin C is a low-molecular-weight protein which has been proposed as a marker of renal function that could replace creatinine. Indeed, the concentration of Cystatin C is mainly determined by glomerular filtration and is particularly of interest in clinical settings where the relationship between creatinine production and muscle mass impairs the clinical performance of creatinine. Since the last decade, numerous studies have evaluated its potential use in measuring renal function in various populations. More recently, other potential developments for its clinical use have emerged. In almost all the clinical studies, Cystatin C demonstrated a better diagnostic accuracy than serum creatinine in discriminating normal from impaired kidney function, but controversial results have been obtained by comparing this protein with other indices of kidney disease, especially serum creatinine-based equations, such as early atherosclerosis, Alzheimer's dementia, vascular aneurysms, hyperhomocysteinaemia and other neurodegenerative diseases. Cystatin C could be a useful clinical tool to identify HIV-infected persons. In addition, its expression is up-regulated in malignance of certain tumor progression.
Cystatin C is a member of family 2 of the cystatin superfamily. It is ubiquitous in human tissues and body fluids and mainly used as a biomarker of kidney function. Cystatin C inhibits many cysteine proteases such as papain and Cathepsins B; H; K; L and S. As an inhibitor of cysteine proteinases; Cystatin C is thought to serve an important physiological role as a local regulator of this enzyme activity. Recently; it has been studied for its role in predicting new-onset or deteriorating cardiovascular disease. It also seems to play a role in brain disorders involving amyloid (a specific type of protein deposition); such as Alzheimer's disease.
Cystatin-D is a protein that in humans is encoded by the CST5 gene. The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes a protein found in saliva and tears. The encoded protein may play a protective role against proteinases present in the oral cavity.
Cystatin-M is a typical secretory protein. It is synthesized as a preprotein with a patent N-terminal signal sequence.It belongs to the cystatin family. The most widely accepted function of cystatins is that of protease inhibitors. Most cysteine proteases are confined within cells where optimal pH and redox conditions favor their enzymatic activity. Thus, the majority of intracellular cysteine proteases are inactivated by oxidizing conditions outside the cells. Among the various types of intracellular cysteine proteases, cystatins seem to target preferentially endosomal/lysosomal cysteine proteases of the papain family, such as cathepsin B, cathepsin K/O2, cathepsin L, cathepsin L2/V and cathepsin S. Another important function of Cst6 seems to be in the terminal differentiation of stratified squamous epithelial cells and in the formation of cornified envelops. Cst6 is believed to be important in fine-tuning the enzymatic activities of endosomal/lysosomal cysteine proteases such as cathepsin L, cathepsin L2/V and AEP/mammalian legumain. Deregulated activity of these proteases could lead to abnormal activation of transglutaminases and disorders in cornification.
Cystatin SA is a member of family 2 of the Cystatin superfamily. Together with Cystatins S and SN, it is produced by the salivary gland and secreted largely in the submandibular/sublingual saliva. Cystatin SA inhibits Cathepsin L, but may not inhibit Cathepsins B and H. The functions of Cystatin SA are largely unknown. However, it has been suggested to play a role in the control of periodontal tissue destruction.
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