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The decrease in GBA activity may influence α-Syn oligomerization, explaining the high risk of PD development in GD patients. © 2015 International Parkinson and Movement Disorder Society.

Administration of dizocilpine (MK-801, noncompetitive antagonist of NMDA glutamate receptors) into the neostriatum decreased the reproducibility and duration of hyperkinesis in rats induced by repeated microinjections of GABA(A) receptor antagonist picrotoxin. By contrast, glutamate potentiated the hyperkinetic and convulsive effect of picrotoxin and promoted the inhibition of conditioned avoidance response. Our results indicate that the striatal glutamatergic system is involved in the development of locomotor and cognitive disorders associated with deficiency of the neostriatal GABAergic system and playing a role in the pathogenesis of Huntington's chorea.