biostudies-literatureDi Benedetto GPRIN from the Italian Ministry of Research.11625https://www.ebi.ac.uk/biostudies/studies/S-EPMC9569968biostudies-literatureUnknown23(19)TRAIL, a member of TNF superfamily, is a potent inducer of neuronal death. Neurotoxic effects of TRAIL appear mediated by its death receptor TRAIL-R2/DR5. To assess the role of TRAIL/TRAIL-R2 pathway in AD-related neurodegeneration, we studied the impact of the treatment with amyloid-β (Aβ) upon cell viability and inflammation in TRAIL-R-deficient mice (TRAIL-R^-/-). Here, we demonstrate that the lack of TRAIL-R2 protects from death cultured TRAIL-R^-/- mouse embryonic hippocampal cells after treatment with either Aβ1-42 or TRAIL. Consistently, stereotaxic injection of Aβ1-42 resulted in blunted caspase activation, as well as in reduction of JNK phosphorylation and increased AKT phosphorylation in TRAIL-R^-/- mice. Moreover, the lack of TRAIL-R2 was associatedInternational journal of molecular sciencesTRAIL-R Deficient Mice Are Protected from Neurotoxic Effects of Amyloid-β.PMC95699682017YH3SXKDi Mauro RCaltabiano RBellanca CMBurgaletto CCantarella GBernardini RMunafo ADi Benedetto GSerapide MFfalseTRAIL-R Deficient Mice Are Protected from Neurotoxic Effects of Amyloid-β.TRAIL, a member of TNF superfamily, is a potent inducer of neuronal death. Neurotoxic effects of TRAIL appear mediated by its death receptor TRAIL-R2/DR5. To assess the role of TRAIL/TRAIL-R2 pathway in AD-related neurodegeneration, we studied the impact of the treatment with amyloid-β (Aβ) upon cell viability and inflammation in TRAIL-R-deficient mice (TRAIL-R^-/-). Here, we demonstrate that the lack of TRAIL-R2 protects from death cultured TRAIL-R^-/- mouse embryonic hippocampal cells after treatment with either Aβ1-42 or TRAIL. Consistently, stereotaxic injection of Aβ1-42 resulted in blunted caspase activation, as well as in reduction of JNK phosphorylation and increased AKT phosphorylation in TRAIL-R^-/- mice. Moreover, the lack of TRAIL-R2 was associated2022-01-01T00:00:00Z2022 Oct2025-04-18T19:32:48.981Z2024-11-06T04:34:51.993ZS-EPMC95699683623293110.3390/ijms231911625