Dataset Information

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

ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Pyramidal Neuron, Hippocampus Pyramidal Layer, Astrocyte

DISEASE(S): Prion Disease

SUBMITTER: Hector Albert Gasco

LAB HEAD: Giovanna Mallucci

PROVIDER: PXD042577 | Pride | 2024-05-24

REPOSITORIES: Pride

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

Albert-Gasco Hector H Smith Heather L HL Alvarez-Castelao Beatriz B Swinden Dean D Halliday Mark M Janaki-Raman Sudha S Butcher Adrian J AJ Mallucci Giovanna R GR

Brain : a journal of neurology 20240201 2

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 n ...[more]

PMID: 37703312

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			Action	DRS
	AHAlabelling_NBH_1.raw	Raw
	AHAlabelling_NBH_2.raw	Raw
	AHAlabelling_RML_1.raw	Raw
	AHAlabelling_RML_2.raw	Raw
	AHAlabelling_Traz_1.raw	Raw