Evidence against a contribution of the CCAAT-enhancer binding protein homologous protein (CHOP) in mediating neurotoxicity in rTg4510 mice.

ABSTRACT: Tau accumulation and progressive loss of neurons are associated with Alzheimer's disease (AD). Aggregation of tau has been associated with endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR). While ER stress and the UPR have been linked to AD, the contribution of these pathways to tau-mediated neuronal death is still unknown. We tested the hypothesis that reducing C/EBP Homologous Protein (CHOP), a UPR induced transcription factor associated with cell death, would mitigate tau-mediated neurotoxicity through the ER stress pathway. To evaluate this, 8.5-month-old male rTg4510 tau transgenic mice were injected with a CHOP-targeting or scramble shRNA AAV9 that also expressed EGFP. Following behavioral assessment, brain tissue was collected at 12 months,

SUBMITTER: Criado-Marrero M 

PROVIDER: S-EPMC9072347 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature