Role of S-palmitoylation of synaptic proteins in DYT1 dystonia

Proponente Stefano Biagioni - Professore Ordinario
Sottosettore ERC del proponente del progetto
Componenti gruppo di ricerca
Componente Categoria
Giancarlo Poiana Componenti strutturati del gruppo di ricerca
Mauro Giorgi Componenti strutturati del gruppo di ricerca
Componente Qualifica Struttura Categoria
SILVIA CARDARELLI COCOCO Biologia e Biotecnologie "Charles Darwin" Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca

Our recent work showed, in the basal ganglia circuit of a transgenic DYT1 mouse model, an altered expression of the enzyme phosphodiesterase 10A (PDE10A). PDE10A is highly enriched in mammalian striatum, specifically in the GABAergic medium spiny neurons, and reaches the output structures of basal ganglia through the axonal transport along the projections of these striatal neurons. Moreover, several studies revealed that PDE10A and many proteins, involved in synaptic transmission, are post-translationally modified through S-palmitoylation. The altered expression of PDE10A and D2 receptor, previously demonstrated in dystonia animal models, could depend on a common modification of lipid post-translational modification that cause a dynamic relocation among different cellular compartments. Therefore, the aim of this project is to study the expression of PDE10A, adenosine (A2A) and dopaminergic (D1 and D2) receptors, that are involved in the synaptic transduction pathways mediated by cyclic nucleotides in the basal ganglia, in the dystonia Tor1a delta gag/+ mouse model. The experimental approach will include immunohistochemistry, confocal microscopy, biochemistry, physiology and the investigation of post-translational S-palmitoyl modification.

LS1_10, LS5_1, LS5_7

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