Targeting glutamatergic synapses in Parkinson's disease

• The strength of glutamatergic signals to the striatum is regulated during PD progression.
• Alteration of glutamate receptors synaptic localization represents a key event in PD pathogenesis.
• Blocking NMDA receptor downstream events show anti-dyskinetic activity in preclinical and clinical studies.

Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons of the substantia nigra and dramatic motor and cognitive impairments. The current knowledge indicates that the strength of glutamatergic signals from the cortex to the striatum is regulated during the progression of the disease. The efficacy of ionotropic glutamate receptors to modulate synaptic transmission in the striatum indicates that modulation of the activity of these receptors may represent a key target to rescue the altered neurotransmission in PD. Preclinical and clinical studies suggest that agents targeting ionotropic glutamate receptors may ameliorate the motor symptoms of PD as well as to reduce the onset of levodopa-induced dyskinetic motor behaviour.