Trazodone is neuroprotective via rescue of dysregulated synaptic and mitochondrial translatomes in neurodegeneration

We aime to discover changes which occur at the hippocampal nascent proteome prion to the neurodegeneration characteristic of prion disease and how this prion signature difer from that of proven neuroprotective drug trazodone hydrochloride. To label the nacent proteome we used non-canonical aminoacid tagging (NCAT) labelling all cell types within the hippocampus with L-azidohomoalanine (AHA) as well as azinorleucine (ANL) to label specifically Camk2a or GFAP neurons or astrocytes respectivly. We gave methionine surrogates mixed in drinking water and soggy mash for 1 week after which animals were sacrificed and both hippocampi extracted. Affinity purification of this samples showed a restoration of Mitochondrial and syaptic proteins decrease with prion disease which 2 week trazdoone treatement restored.