caa a22 4500 477038174 CHVBK 20180405111310.0 cr unu---uuuuu 170330e19960201xx s 000 0 eng 10.1007/BF02740748 doi (NATIONALLICENCE)springer-10.1007/BF02740748 Glutamate and Parkinson's disease [Elektronische Daten] [Fabio Blandini, Richard Porter, J. Greenamyre] Altered glutamatergic neurotransmission and neuronal metabolic dysfunction appear to be central to the pathophysiology of Parkinson's disease (PD). The substantia nigra pars compacta—the area where the primary pathological lesion is located—is particularly exposed to oxidative stress and toxic and metabolic insults. A reduced capacity to cope with metabolic demands, possibly related to impaired mitochondrial function, may render nigral neurons highly vulnerable to the effects of glutamate, which acts as a neurotoxin in the presence of impaired cellular energy metabolism. In this way, glutamate may participate in the pathogenesis of PD. Degeneration of dopamine nigral neurons is followed by striatal dopaminergic denervation, which causes a cascade of functional modifications in the activity of basal ganglia nuclei. As an excitatory neurotransmitter, glutamate plays a pivotal role in normal basal ganglia circuitry. With nigrostriatal dopaminergic depletion, the glutamatergic projections from subthalamic nucleus to the basal ganglia output nuclei become overactive and there are regulatory changes in glutamate receptors in these regions. There is also evidence of increased glutamatergic activity in the striatum. In animal models, blockade of glutamate receptors ameliorates the motor manifestations of PD. Therefore, it appears that abnormal patterns of glutamatergic neurotransmission are important in the symptoms of PD. The involvement of the glutamatergic system in the pathogenesis and symptomatology of PD provides potential new targets for therapeutic intervention in this neuro-degenerative disorder. Humana Press Inc, 1996 Basal ganglia nationallicence excitotoxicity nationallicence excitatory amino acids nationallicence bioenergetics nationallicence N -methyl- D -aspartate nationallicence Blandini Fabio Neurological Institute "C. Mondino,”, University of Pavia, Pavia, Italy aut Porter Richard University Department of Clinical Neuropathology, Radcliffe Infirmary, Oxford, UK aut Greenamyre J. Departments of Neurology and Pharmacology, Atlanta, GA aut Molecular Neurobiology Humana Press 12/1(1996-02-01), 73-94 0893-7648 12:1<73 1996 12 12035 https://doi.org/10.1007/BF02740748 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02740748 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Blandini Fabio Neurological Institute "C. Mondino,”, University of Pavia, Pavia, Italy aut NATIONALLICENCE 700 1- Porter Richard University Department of Clinical Neuropathology, Radcliffe Infirmary, Oxford, UK aut NATIONALLICENCE 700 1- Greenamyre J. Departments of Neurology and Pharmacology, Atlanta, GA aut NATIONALLICENCE 773 0- Molecular Neurobiology Humana Press 12/1(1996-02-01), 73-94 0893-7648 12:1<73 1996 12 12035 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer