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Titolo:
EXCITOTOXICITY AND NITRIC-OXIDE IN PARKINSONS-DISEASE PATHOGENESIS
Autore:
BEAL MF;
Indirizzi:
MASSACHUSETTS GEN HOSP,NEUROL SERV WARREN 408,NEUROCHEM LAB,32 FRUIT ST BOSTON MA 02114 HARVARD UNIV,SCH MED BOSTON MA 00000
Titolo Testata:
Annals of neurology
fascicolo: 3, volume: 44, anno: 1998, supplemento:, 1
pagine: 110 - 114
SICI:
0364-5134(1998)44:3<110:EANIPP>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
METHYL-D-ASPARTATE; 1-METHYL-4-PHENYLPYRIDINIUM ION MPP+; MPTP-INDUCED NEUROTOXICITY; SUBSTANTIA-NIGRA; GLUTAMATE NEUROTOXICITY; DOPAMINE DEPLETION; KNOCKOUT MICE; MK-801 FAILS; CELL-DEATH; BLACK MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
M.F. Beal, "EXCITOTOXICITY AND NITRIC-OXIDE IN PARKINSONS-DISEASE PATHOGENESIS", Annals of neurology, 44(3), 1998, pp. 110-114

Abstract

A potential role for excitotoxic processes in Parkinson's disease (PD) has been strengthened by the recent observations that there appears to be a mitochondrially encoded defect in complex I activity of the electron transport chain. An impairment of oxidative phosphorylation will enhance vulnerability to excitotoxicity. Substantia nigra neurons possess N-methyl-D-aspartate receptors and there are glutamatergic inputs into the substantia nigra from both the cerebral cortex and the subthalamic nucleus. After activation of excitatory amino acid receptors, there is an influx of calcium followed by activation of neuronal nitric oxide (NO) synthase, which can then lead to the generation of peroxynitrite. Consistent with such a mechanism, studies of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity in both mice and primates have shown that inhibition of neuronal NO synthase exerts neuroprotective effects. Studies utilizing excitatory amino acid receptor antagonists have been inconsistent in mice but show significant neuroprotectiveeffects in primates. These results raise the prospect that excitatoryamino acid antagonists for neuronal NO synthase inhibitors might be useful in the treatment of PD.

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Documento generato il 07/07/20 alle ore 21:28:21