Trazodone rescues dysregulated synaptic and mitochondrial nascent proteomes in prion neurodegeneration.

ABSTRACT: The unfolded protein response (UPR) is rapidly gaining momentum as a therapeutic target for protein misfolding neurodegenerative diseases, in which its overactivation results in sustained translational repression leading to synapse loss and neurodegeneration. In mouse models of these disorders, from Alzheimer's to prion disease, modulation of the pathway-including by the licensed drug, trazodone-restores global protein synthesis rates with profound neuroprotective effects. However, the precise nature of the translational impairment, in particular the specific proteins affected in disease, and their response to therapeutic UPR modulation are poorly understood. We used non-canonical amino acid tagging (NCAT) to measure de novo protein synthesis in the brains of prion-diseased mice with and w

SUBMITTER: Albert-Gasco H 

PROVIDER: S-EPMC10834243 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature