TRAIL (TNF-Related Apoptosis-Inducing Ligand) is encoded by the TNFSF10 gene on chromosome 3q26. It is a type II transmembrane protein belonging to the TNF superfamily that selectively induces apoptosis in transformed and stressed cells while sparing normal cells. TRAIL signaling is implicated in neurodegenerative diseases through its role in regulating neuronal survival, microglial activation, and inflammatory responses.
| Receptor | Expression | Function | [1]
|----------|------------|----------| [2]
| TRAIL-R1 (DR4) | Broad | Pro-apoptotic |
| TRAIL-R2 (DR5) | Broad | Pro-apoptotic |
| TRAIL-R3 (DcR1) | Normal cells | Decoy receptor |
| TRAIL-R4 (DcR2) | Normal cells | Decoy receptor |
| OPG | Various | Decoy receptor |
Neuronal Apoptosis
Microglial Activation
Therapeutic Potential
| Agent | Status | Mechanism |
|---|---|---|
| Dulanermin (APO2L/TRAIL) | Clinical trials | Recombinant TRAIL |
| Anti-DR5 antibodies | Clinical trials | DR5 aggregation |
| Agent | Status | Mechanism |
|---|---|---|
| RANK-Fc | Research | Decoy receptor |
| TRAIL-neutralizing antibodies | Research | Block TRAIL |
Herr et al. TRAIL in AD. Brain Research Reviews. 2009. ↩︎
Werner et al. TRAIL in ALS. Neurobiology of Disease. 2008. ↩︎