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 Slenter

Activity

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

neurodegenerative pathway

Disease Ontology

Alzheimer's disease Parkinson's disease

Cell Type Ontology

retinal pigment epithelial cell

Participants

Label Type Compact URI Comment
NPD1 Metabolite chebi:138655
PP2A Protein uniprot:P62714
TNFR1 Protein uniprot:P19438
Bcl-xL Protein uniprot:Q07817-1
BAX Protein uniprot:Q07812
BIRC3 Protein uniprot:Q13489
Caspase-9 Protein uniprot:P55211
RIP3 Protein uniprot:Q9Y572
Cytochrome c Protein uniprot:P99999
TRAF2 Protein uniprot:Q12933
Bcl-xL Protein uniprot:Q07817-1
Caspase-3 Protein uniprot:P42574
FADD Protein uniprot:Q13158
Caspase-8 Protein uniprot:Q14790
Caspase-7 Protein uniprot:P55210
TRADD Protein uniprot:Q15628
BAX Protein uniprot:Q07812
TNF alpha Protein uniprot:P01375
Bcl-xL Protein uniprot:Q07817-1
RIP1 Protein uniprot:Q13546
TNFR1 Protein uniprot:P19438
TRAF2 Protein uniprot:Q12933
TRADD Protein uniprot:Q15628
TNF alpha Protein uniprot:P01375
RIP1 Protein uniprot:Q13546
TRADD Protein uniprot:Q15628
TRAF2 Protein uniprot:Q12933
RIP1 Protein uniprot:Q13546
RIP3 Protein uniprot:Q9Y572

References

  1. 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