Prospects of glutamate antagonists in the therapy of Parkinson's disease.
It has been suggested that the excitatory amino acid glutamate, acting as both a neurotoxin and a neurotransmitter, might play a central role in the pathophysiology of Parkinson's disease (PD). Intrinsic energetic defects of the neurons of the substantia nigra pars compacta, the brain area where the degenerative process of PD takes place, may render nigral neurons highly vulnerable to the effects of glutamate, which acts as a neurotoxin in the presence of impaired cellular energy metabolism. Degeneration of dopamine nigral neurons and striatal dopaminergic denervation cause a cascade of functional modifications in the activity of basal ganglia nuclei. Due to the close relationship that links dopaminergic and glutamatergic neurotransmission, glutamate is directly involved in the functional alterations of basal ganglia circuitry that lead to the development of parkinsonian motor symptoms. Drugs counteracting the effects of glutamate might therefore provide new protective and symptomatic strategies for therapy of PD.
Blandini
F
F
Laboratory of Functional Neurochemistry, C Mondino Foundation, Pavia, Italy.
Greenamyre
J T
JT
D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D000978:Antiparkinson Agents; D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid