Pro-survival signaling of neuroprotectin D1 (WP5182)
Homo sapiens
Uncompensated oxidative stress triggers neuroprotectin D1 to inhibit caspase activity via the intrinsic mitochondrial pathway and via the stimulation of BIRC3 leading to pro-survival stimuli. By inhibiting the formation of the Bax/Bcl-xL complex in the mitochondrial membrane, NPD1 decreases the release of Cytochrome c leading to a lower pro-apoptotic activity. Furthermore, NPD1 inhibits the internalization of death-inducing signaling complex (DISC) which is involved in the initiation of apoptosis, thereby promoting survival of the cell. The neuroprotective effect of NPD1 therefore contributes to the management of diseases like Alzheimer’s disease, stroke, age-related macular degeneration, traumatic brain injury, Parkinson’s disease and other neurodegenerations.
Authors
Luc Hooglugt , Eric Weitz , Jesper , and Denise SlenterActivity
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Organisms
Homo sapiensCommunities
Annotations
Disease Ontology
Alzheimer's disease Parkinson's diseaseCell Type Ontology
retinal pigment epithelial cellPathway Ontology
neurodegenerative pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| NPD1 | Metabolite | chebi:138655 | |
| PP2A | Protein | uniprot:P62714 | |
| TNFR1 | Protein | uniprot:P19438 | |
| BCL2L1 | Protein | uniprot:Q07817-1 | 'Bcl-xL' originally |
| BIRC3 | Protein | uniprot:Q13489 | |
| CASP9 | Protein | uniprot:P55211 | 'Caspase-9' originally |
| RIP3 | Protein | uniprot:Q9Y572 | |
| CYCS | Protein | uniprot:P99999 | 'Cytochrome c' originally |
| TRAF2 | Protein | uniprot:Q12933 | |
| CASP3 | Protein | uniprot:P42574 | 'Caspase-3' originally |
| FADD | Protein | uniprot:Q13158 | |
| CASP8 | Protein | uniprot:Q14790 | 'Caspase-8' originally |
| CASP7 | Protein | uniprot:P55210 | |
| TRADD | Protein | uniprot:Q15628 | |
| BAX | Protein | uniprot:Q07812 | |
| TNF | Protein | uniprot:P01375 | |
| RIP1 | Protein | uniprot:Q13546 |
References
- Molecular mechanisms of signaling via the docosanoid neuroprotectin D1 for cellular homeostasis and neuroprotection. Asatryan A, Bazan NG. J Biol Chem. 2017 Jul 28;292(30):12390–7. PubMed Europe PMC Scholia