NMD receptor modulation in early Parkinsonism and L-DOPA-induced discinesia: a new therapeutic strategy

The project will focus on the study of the molecular composition of the glutamatergic synapse in control rats, in parkinsonian partially lesioned rats and in L-DOPA-treated early and advanced PD animals, in presence or absence of chronic treatment with cell-permeable TAT peptide fused to NR2A 9aa C-terminal domain (Tat-2A) able to disrupt PSD-MAGUKs/NR2A interaction. Molecular composition of NMDA receptor complex will be also evaluated in sham-operated rats treated with the Tat-2A peptide. Immunoprecipitation analysis will be performed to study modifications of NR2A/2B subunits interaction with each PSD-MAGUK member in early PD rats and in L-DOPA-treated rats as well as to confirm the effect of Tat-2A treatment on PSD-MAGUKs/NR2A interaction.