Cathepsin S Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Attribute | Value | [1]
|-----------|-------| [2]
| Protein Name | Cathepsin S |
| Gene Symbol | CTSS |
| UniProt ID | P25774 |
| PDB Structures | 1MS6, 1NQR, 1GLO, 2JPG |
| Molecular Weight | 37.5 kDa (proenzyme), 24.5 kDa (mature) |
| Subcellular Localization | Lysosomes, secreted |
| Protein Family | Papain family cysteine proteases |
Cathepsin S is a potent lysosomal cysteine protease with unique features that distinguish it from other cathepsins: it retains proteolytic activity at neutral pH and can be secreted extracellularly.[1] These properties make cathepsin S important in antigen presentation, extracellular matrix degradation, and various disease processes including Alzheimer's disease, multiple sclerosis, and cancer.
Cathepsin S is synthesized as a preproenzyme:
| PDB ID | Description | Resolution |
|---|---|---|
| 1MS6 | Native structure | 2.0 Å |
| 1NQR | With inhibitor | 1.8 Å |
| 1GLO | Complex with cystatin | 2.3 Å |
| 2JPG | Active site mutant | 2.1 Å |
Cathepsin S cleaves various substrates:[2]
Antigen Presentation
Extracellular Proteolysis
Cell Signaling
Cathepsin S has complex roles in AD:[3]
Cathepsin S is a drug target:[4]
| Strategy | Compound | Stage |
|---|---|---|
| Inhibitors | MIV-247, LHVS | Preclinical |
| Antibodies | Rymovutide | Clinical trials |
| Selectivity | Over cathepsins B, L | Challenge |
The study of Cathepsin S Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Xu J, et al. "Cathepsin S activity in Alzheimer's disease." J Neurochem. 2019;151(4):491-504. J Neurochem. 2019. ↩︎
Liao Y, et al. "Targeting cathepsin S for Alzheimer's disease therapy." Front Aging Neurosci. 2021;13:756890. Front Aging Neurosci. 2021. ↩︎