Cathepsins: Proteases that are vital for survival but can also be fatal

Abstract

The state of enzymes in the human body determines the normal physiology or pathology, so all the six classes of enzymes are crucial. Proteases, the hydrolases, can be of several types based on the nucleophilic amino acid or the metal cofactor needed for their activity. Cathepsins are proteases with serine, cysteine, or aspartic acid residues as the nucleophiles, which are vital for digestion, coagulation, immune response, adipogenesis, hormone liberation, peptide synthesis, among a litany of other functions. But inflammatory state radically affects their normal roles. Released from the lysosomes, they degrade extracellular matrix proteins such as collagen and elastin, mediating parasite infection, autoimmune diseases, tumor metastasis, cardiovascular issues, and neural degeneration, among other health hazards. Over the years, the different types and isoforms of cathepsin, their optimal pH and functions have been studied, yet much information is still elusive. By taming and harnessing cathepsins, by inhibitors and judicious lifestyle, a gamut of malignancies can be resolved. This review discusses these aspects, which can be of clinical relevance.

Keywords: Carcinogenesis; Cathepsin; Extracellular matrix; Immune activation; Inflammation; Inhibitors.

Fig. 1

Cathepsins are necessary evils, like other proteases. They are present in extracellular matrix, lysosome, melanosome. In normal physiological condition, they play role in digestion, coagulation, immune response, adipogenesis, hormone liberation, peptide synthesis, autophagy. But, in inflammatory condition they can pave the path for cancer, cardiac disease, arthritis, pregnancy loss, among other diseases.