Effect of rasagiline on the molecular composition of the excitatory postsynaptic density

In the last decade, several neuroprotective therapies have been proposed for Parkinson's disease and rasagiline was indicated as one of the most promising candidates by preclinical studies. The drug has already been tested in phase III clinical studies (the ADAGIO study). The mechanism underlying rasagiline-dependent neuroprotection is complex and almost unknown. Here, we show that rasagiline is involved in the regulation of the molecular composition of the postsynaptic density of glutamatergic synapses. In hippocampus as well as in striatum, rasagiline induces a significant reduction of synaptic levels of NR2A-containing NMDA receptors and in hippocampal slices it also significantly decreases synaptic levels of GluR1-containing AMPA receptors. This capability of rasagiline to modulate ionotropic glutamate receptors composition at synaptic sites strengthens the rationale for its clinical use to slow the progression of Parkinson's disease.