Journey of cystatins from being mere thiol protease inhibitors to at heart of many pathological conditions

Abstract

Cystatins are thiol proteinase inhibitors (TPI), present ubiquitously in animals, plants and micro-organisms. These are not merely inhibitors rather they are at heart of many pathological conditions ranging from diabetes to renal failure. These are essential for maintenance of protein balance of the cell; once this balance gets disturbed, it may lead to cell death. Thus, cystatins cannot be merely regarded as TPI's as these have been found to play a pivotal role in tumorigenesis and neurodegenerative diseases. Many studies have reported the variation in cystatin level in incidences of different types of cancer; highlighting an important role played by these inhibitors in cancer development and progression. Cystatin C is increasingly replacing creatinine as a biomarker of glomerular filtration rate (GFR) thereby highlighting the importance of this important inhibitor. Some recent studies have also reported the interaction pattern of various anti-cancer drugs with cystatins in a bid to find how these drugs affect this important inhibitors and whether these drugs have any side effect on cystatins. Thus, in this growing disease era it can be said that cystatins are no more just inhibitors blocking the activity of thiol proteases rather they play a pivotal role in variety of pathological conditions.

Proteomic analysis of dentin–enamel junction and adjacent protein‐containing enamel matrix layer of healthy human molar teeth

“…Cystatins are thiol proteinase inhibitors, present ubiquitously in living organisms, including humans. Many studies have reported a variation in cystatin levels in different diseases, such as cancer, and it has been suggested that cystatins play a pivotal role in a variety of pathological conditions . The roles of cystatins in saliva have been investigated in several studies .…”

Crouching Tiger, Hidden Protein: Searching for Insecticidal Toxins in Venom of the Red Tiger Assassin Bug (Havinthus rufovarius)

“…The major component of the other insecticidal fraction isolated, H. rufovarius venom cystatin 1, is a member of the cystatin cysteine protease inhibitor family that occurs in diverse animals, plants, and micro-organisms [ 18 ]. Cystatins have been identified in the venoms of various snakes, including the Australian lowland copperhead ( Austrelaps superbus ) [ 19 ].…”

Utility of the Serum Cystatin C Level for Diagnosis of Osteoporosis among Middle-Aged and Elderly People

“…Serum cystatin C level correlates with glomerular filtration rate [23], which is an important marker of kidney health and determinant of the progression of both diabetes and chronic kidney disease [25, 26]. Given its biological importance, serum cystatin C has also been linked to a number of other diseases [27].…”