What Is a Cysteine Protease Inhibitor?

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  • Written By: Haven Lee
  • Edited By: A. Joseph
  • Last Modified Date: 16 September 2019
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Cysteine protease is an enzyme that breaks down chains of amino acids that make up protein known as polypeptides. A cysteine protease inhibitor is a substance that targets this enzyme. Pathogens are shown to use cysteine proteases in their mechanisms of action. Evidence indicates that cysteine proteases play a role in cancer proliferation, osteoporosis, Alzheimer's disease, arthritis and microbial infections. By blocking this enzyme, a cysteine protease inhibitor might be an important tool in the effort to combat these conditions.

Papain, cathepsin, caspase and calpain are the primary cysteine proteases found in plants and animals. A cysteine protease inhibitor is a protein that can help neutralize undesirable cysteine protease activity. Some of these inhibitors block protease sites to prevent access, and others force the enzyme to self-destruct.

Cells have several strategies to protect themselves against malignant protease activity. Apoptosis inhibitors are a family of proteins that interfere with programmed cell death. These proteins act as cysteine protease inhibitors by binding to caspase and inhibiting its functioning. A number of viruses rely on caspase activity to flourish.

Cystatin proteins are composed of a diverse group of cysteine protease inhibitors that protect tissues from the destruction caused by pathogenic cysteine proteases. Researchers isolated the first cysteine protease inhibitor of this type from a chicken egg. Cystatin is shown to inhibit the cysteine proteases papain and cathepsin.


Another family of proteins that act as cysteine protease inhibitors are serpins. This class of proteins employ a unique suicide-like mechanism to inhibit papain and cathepsin. Serpins recognize, then bind to cysteine proteases and irreversibly change their structure. This mutation prevents the protease from functioning normally. Scientists have identified more than three dozen serpin proteins in the human body.

Studies have indicated that cysteine protease inhibitors cause a significant reduction in parasite proliferation. Parasites produce cysteine proteases that appear to play roles in modulating the invasion and destruction of tissue. The resistant nature of some parasites has led researchers to examine a different approach. Cysteine protease inhibitors might provide an alternative treatment for drug-resistant parasitic infections.

Researchers have explored the potential use of cysteine protease inhibitors for combating Alzheimer's disease. Abnormal accumulation of beta-amyloid peptides in the brain plays a role in the progression of this condition. In animal studies, cysteine protease inhibitors have reduced beta-amyloid peptide brain levels by as much as 70 percent by blocking cathepsin B. This effect results in improved memory deficits associated with Alzheimer's disease.


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