Cysteine cathepsins and extracellular matrix degradation

Area of Science:

• Biochemistry
• Molecular Biology
• Pathology

Background:

• Cysteine cathepsins function in intracellular protein turnover within lysosomes.
• Extracellular secretion of cysteine cathepsins is linked to various physiological and disease states.
• Their role in in vivo extracellular matrix (ECM) degradation has become increasingly recognized.

Purpose of the Study:

• To review the extracellular functions of cysteine cathepsins in ECM degradation.
• To discuss the regulation of cathepsin activity, particularly in acidic microenvironments.
• To examine ECM substrates like collagen and elastin and their pathological relevance.

Main Methods:

• Focus on cysteine cathepsins and their extracellular roles.
• Analysis of ECM substrates, including collagen and elastin.
• Overview of cathepsin inhibitors in clinical development for ECM-related diseases.

Main Results:

• Cysteine cathepsins are significant proteases in ECM remodeling, with roles beyond degradation.
• Their deregulated activity is implicated in numerous ECM-linked diseases.
• Cathepsins S and K are identified as key therapeutic targets, with Cathepsin K being prominent for osteoporosis.

Conclusions:

• Cysteine cathepsins are crucial therapeutic targets for ECM-related diseases like osteoporosis, cancer, and cardiovascular diseases.
• Cathepsin K is a major target for osteoporosis, with related drugs in advanced clinical trials.
• This review is part of a special issue on matrix-mediated cell behavior.