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In-Depth Information
whereas the extralysosomal neutral pH, oxidative and endogenous inhibitor-rich
milieu is prohibitive for cathepsin activity. However, under conditions that allow an
acidic pH in the ECM, such as within the resorption lacuna underneath osteoclasts,
a potent extracellular activity is possible. Moreover, certain pathologies show an
overexpression of cathepsins, and when accompanied by pericellular acidification
and a reduction of extracellular cystatin expression this can lead to a highly
destructive cocktail of conditions which may cause dramatic tissue damage. Selec-
tive cathepsin inhibitors might thus be highly beneficial to control these “out-
of-place” proteases.
Acknowledgments Support: DB: Canada Research Award and Canadian Institutes of Health
Research grants: MOP 86586, MOP 6447, and 89974.
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