title: Some molecular mechanisms of dopaminergic and glutamatergic dysfunctioning in Parkinson's disease.
abstract: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder with a considerable socioeconomic burden. The pathomechanism of PD clearly involves the synergistic interaction of dopaminergic and glutamatergic dysfunctioning, including maladaptive corticostriatal synaptoplasticity. Most of the available treatment options have the aim of restoration of the physiological dopaminergic activity. Currently, the most widely used treatment is L-3,4-dihydroxyphenylalanine (L-DOPA), which leads to the best symptomatic relief in PD. However, the long-term use of L-DOPA results in abnormal involuntary movements in almost all cases, the development of these dyskinetic movements also involving maladaptive corticostriatal synaptoplasticity. Perhaps chronic L-DOPA treatment has neurotoxic effects as well, but it has not yet been proved in clinical studies. Another important group of dopamine replacement therapy (DRT)-related side-effects consists of disinhibitory psychopathologies. Recent studies revealed that genetic polymorphisms affecting certain dopaminergic and glutamatergic receptors serve as independent risk factors for the development of these pathological conditions in PD patients. The available scientific data demonstrate that alterations in the kynurenine pathway of the tryptophan metabolism can be observed in PD and these alterations may contribute to the disease pathogenesis and to the occurrence of DRT-related side-effects. Therapeutic strategies that target the restoration of the kynurenine metabolism could therefore hold promise.
authors.affiliation: Department of Neurology, Albert Szent-Györgyi Clinical Centre, University of Szeged, Semmelweis u. 6, 6725, Szeged, Hungary.
authors.forename: Dénes
authors.initials: D
authors.lastname: Zádori
authors.forename: Levente
authors.initials: L
authors.lastname: Szalárdy
authors.forename: József
authors.initials: J
authors.lastname: Toldi
authors.forename: Ferenc
authors.initials: F
authors.lastname: Fülöp
authors.forename: Péter
authors.initials: P
authors.lastname: Klivényi
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
mesh_terms: D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000627:therapeutic use; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D015259:Dopamine Agents; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D004298:Dopamine