Caspase 3 (Casp3) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Caspase 3 (CASP3) is an executioner caspase that executes the final stages of apoptosis. It is encoded by the CASP3 gene located on chromosome 4q34 and is one of the most studied caspases in neurodegeneration research.
| Caspase 3 | |
|---|---|
| Gene Symbol | CASP3 |
| Full Name | Caspase 3 |
| Chromosome | 4q34 |
| NCBI Gene ID | 837 |
| OMIM | 600636 |
| Ensembl ID | ENSG00000164305 |
| UniProt ID | P42574 |
Caspase-3 exists as an inactive zymogen (procaspase-3) that requires proteolytic cleavage for activation. It is activated by both the intrinsic (mitochondrial) and extrinsic (death receptor) pathways:
Activated caspase-3 (p17/p11 heterodimer) cleaves numerous cellular substrates:
Caspase-3 plays multiple roles in AD pathogenesis:
In PD, caspase-3 mediates dopaminergic neuron death:
Caspase-3 is elevated in ALS:
Following cerebral ischemia or trauma:
Caspase-3 inhibitors have been extensively studied:
| Agent | Mechanism | Status | Disease |
|---|---|---|---|
| Z-DEVD-FMK | Irreversible inhibitor | Preclinical | Stroke, TBI |
| Ac-DEVD-CHO | Reversible inhibitor | Research | Neuroprotection |
| M826 | Caspase-3 selective | Research | AD |
Note: Pan-caspase inhibitors may have adverse effects; selective targeting is preferred.
| Disease | Role | Evidence |
|---|---|---|
| Alzheimer's Disease | Synaptic loss, tau cleavage | Elevated in AD brain[1] |
| Parkinson's Disease | Neuronal death | Active caspase-3 in SN[3] |
| ALS | Motor neuron death | Activated in ALS models |
| Stroke | Ischemic injury | Mediates neuronal death |
CASP3 is ubiquitously expressed in the brain:
[1] Shimohama S, et al. Activation of caspase-3 in the brains of patients with Alzheimer's disease. Biochem Biophys Res Commun. 1999.
[2] Gamblin TC, et al. Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer's disease. Proc Natl Acad Sci USA. 2003.
[3] Tatton NA. Increased caspase 3 and Bax immunoreactivity accompany nuclear GAPDH translocation and neuronal apoptosis in Parkinson's disease. Exp Neurol. 2000.
The study of Caspase 3 (Casp3) 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.
[1] Shimohama S, et al. Activation of caspase-3 in the brains of patients with Alzheimer's disease. Biochem Biophys Res Commun. 1999;258(2):401-406.
[2] Gamblin TC, et al. Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer's disease. Proc Natl Acad Sci USA. 2003;100(17):10032-10037.
[3] Tatton NA. Increased caspase 3 and Bax immunoreactivity accompany nuclear GAPDH translocation and neuronal apoptosis in Parkinson's disease. Exp Neurol. 2000;166(1):29-43.