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• W4367295846 abstract "Abstract Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease and arises from dopamine (DA) neuron death selectively in the substantia nigra pars compacta (SNc) . Rit2 is a reported PD risk allele, and recent single cell transcriptomic studies identified a major RIT2 cluster in PD DA neurons, potentially linking Rit2 expression anomalies to a PD patient cohort. However, it is still unknown whether Rit2 loss itself is causative for PD or PD-like symptoms. Here we report that conditional Rit2 silencing in mouse DA neurons drove a progressive motor dysfunction that was more rapid in males than females and was rescued at early stages by either inhibiting the DA transporter (DAT) or with L-DOPA treatment. Motor dysfunction was accompanied by decreases in DA release, striatal DA content, phenotypic DAergic markers, and a loss of DA neurons, with increased pSer129-alpha synuclein expression. These results provide the first evidence that Rit2 loss is causal for SNc cell death and a PD-like phenotype, and reveal key sex-specific differences in the response to Rit2 loss." @default.
• W4367295846 created "2023-04-29" @default.
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• W4367295846 date "2023-04-28" @default.
• W4367295846 modified "2023-10-01" @default.
• W4367295846 title "Rit2 loss in dopaminergic neurons drives a progressive Parkinsonian phenotype" @default.
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• W4367295846 doi "https://doi.org/10.1101/2023.04.26.538430" @default.
• W4367295846 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37162843" @default.
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