Caspase 8 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-8 is encoded by the CASP8 gene. It is a Caspase family, initiator caspases involved in caspase-8 mediates extrinsic apoptosis by death receptors (fas/cd95, trail-r1/2, tnfr1). it can also...
| Caspase-8 | |
|---|---|
| Protein Name | Caspase-8 |
| Gene | CASP8 |
| UniProt ID | Q14790 |
| PDB ID(s) | 1K7J, 1K8A, 2C7E, 2C7F, 3K7E, 4JJU, 4PSV |
| Molecular Weight | 55.4 kDa |
| Subcellular Localization | Cytoplasm, Cell Membrane |
| Protein Family | Caspase family, initiator caspases |
Caspase-8 exists as two isoforms (Caspase-8a and Caspase-8b) that differ by 2 amino acids. It has a long prodomain with two death effector domains (DEDs).
Caspase-8 mediates extrinsic apoptosis by death receptors (Fas/CD95, TRAIL-R1/2, TNFR1). It can also initiate a caspase cascade independent of mitochondria (Type I cells) or cleave Bid to engage the intrinsic pathway (Type II cells). Caspase-8 also has non-apoptotic roles in cell proliferation and differentiation.
Death receptor signaling contributes to neuronal apoptosis in AD.
Caspase-8 is activated by DJ-1 loss and contributes to dopaminergic neuron death.
Extrinsic apoptotic pathway contributes to ischemic neuronal injury.
Death receptor-mediated caspase-8 activation contributes to secondary injury.
Caspase-8 inhibitors (IETD-FMK) have shown neuroprotective potential in preclinical models of stroke and TBI.
[1] Protein information and structure. UniProt Database.
Caspase-8 is activated by the death receptor pathway through a well-characterized cascade:
Caspase-8 has important non-apoptotic roles:
| Compound | Type | Status | Notes |
|---|---|---|---|
| Z-IETD-FMK | Peptide inhibitor | Research tool | Selective for caspase-8 |
| A-385,358 | Small molecule | Preclinical | Brain-penetrant |
| Emricasan | Pan-caspase inhibitor | Clinical trials | Not specific to caspase-8 |
The study of Caspase 8 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.
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[1] Protein information. UniProt Database.