Casp3 Protein — Caspase 3 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Protein Name | Caspase-3 |
|---|---|
| Gene | [CASP3](/genes/casp3) |
| UniProt ID | [P42574](https://www.uniprot.org/uniprot/P42574) |
| Protein Size | 277 amino acids (active enzyme); full-length pro-Caspase-3 is 320 aa (~35 kDa) |
| Subcellar Localization | Cytoplasm; cleaves substrates in both cytosol and nucleus |
| Protein Family | Cysteine-aspartic proteases (caspases); executioner caspases |
| PDB Structures | [1CP3](https://www.ebi.ac.uk/pdbe/search/pdb/1CP3), [1R2X](https://www.ebi.ac.uk/pdbe/search/pdbX/1R2), [2J30](https://www.ebi.ac.uk/pdbe/search/pdb/2J30) |
Caspase-3 is the primary executioner caspase in the apoptosis pathway, responsible for the proteolytic cleavage of numerous cellular substrates that lead to the characteristic morphological and biochemical features of programmed cell death. It plays a central role in both extrinsic and intrinsic apoptotic pathways.
Caspase-3 has a characteristic caspase structure:
The protease adopts a classic caspase fold with a central six-stranded β-sheet flanked by five α-helices.
Caspase-3 performs critical functions in:
Apoptosis Execution: Cleaves numerous substrates (~2,000+ known targets) that execute the apoptotic program[1].
DNA Fragmentation: Cleaves ICAD/DFF45, releasing CAD endonuclease for DNA fragmentation.
Cytoskeletal Reorganization: Cleaves actin, tubulin, and cytoskeletal proteins for membrane blebbing.
Membrane Flip: Cleaves flippase inhibitors, exposing phosphatidylserine for phagocytic recognition.
Cell Cycle Arrest: Cleaves proteins involved in cell cycle progression.
Non-Apoptotic Functions:
Caspase-3 activation is a hallmark of AD neurons:
Caspase-3 contributes to dopaminergic neuron death:
Caspase-3 activation in motor neurons:
Caspase-3 is the key executor of post-ischemic neuronal death:
Caspase-3 is a major therapeutic target:
Note: Broad-spectrum caspase inhibitors have shown neuroprotective effects in animal models but clinical trials have been limited by toxicity and narrow therapeutic windows.
CASP3 interacts with:
The study of Casp3 Protein — Caspase 3 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.