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Titolo:
ISOQUINOLINE NEUROTOXINS IN THE BRAIN AND PARKINSONS-DISEASE
Autore:
NAGATSU T;
Indirizzi:
FUJITA HLTH UNIV,SCH MED,INST COMPREHENS MED SCI TOYOAKE AICHI 47011 JAPAN
Titolo Testata:
Neuroscience research
fascicolo: 2, volume: 29, anno: 1997,
pagine: 99 - 111
SICI:
0168-0102(1997)29:2<99:INITBA>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHROMATOGRAPHY-MASS-SPECTROMETRY; N-METHYLISOQUINOLINIUM ION; STRUCTURALLY RELATED-COMPOUNDS; TYROSINE-HYDROXYLASE ACTIVITY; STRIATAL TISSUE-SLICES; MONOAMINE-OXIDASE; RAT-BRAIN; 1-METHYL-4-PHENYLPYRIDINIUM ION; DOPAMINERGIC NEUROTOXIN; MOUSE-BRAIN;
Keywords:
COMPLEX I; DOPAMINE; NIGROSTRIATAL NEURONS; ISOQUINOLINES; MONOAMINE OXIDASE; PARKINSONS DISEASE; TYROSINE 3-MONOOXYGENASE (TYROSINE HYDROXYLASE);
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
89
Recensione:
Indirizzi per estratti:
Citazione:
T. Nagatsu, "ISOQUINOLINE NEUROTOXINS IN THE BRAIN AND PARKINSONS-DISEASE", Neuroscience research, 29(2), 1997, pp. 99-111

Abstract

Parkinson's disease is thought to be caused by some unknown endogenous or exogenous factors interacting with genetic dispositions. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an exogenous neurotoxinproducing parkinsonism in humans, monkeys and various animals as the result of monoamine oxidase type B (MAO-B)-catalyzed conversion of it to the 1-methyl-4-phenyl-pyridinium ion (MPP+), which selectively kills the nigrostriatal dopaminergic neurons. Various isoquinoline derivatives were found in the brain of patients with Parkinson's disease. Isoquinoline derivatives have neurochemical properties similar to those of MPTP and they are considered to be the endogenous neurotoxins which cause Parkinson's disease. Among them, tetrahydroisoquinoline (TIQ), 1-benzyl-TIQ, and (R)-1,2-dimethyl-5,6-dihydroxy-TIQ [(R)-N-methyl-salsolinol)] have the most potent neurotoxicity. TIQs, like MPTP, may be activated via N-methylation by N-methyltransferase and oxidation by MAO. TIQs as well as MPP+ inhibit complex I of the electron transport system in mitochondria, thereby reducing ATP formation and producing oxygen radicals. Although the properties of TIQs are similar to those of MPTP, the neurotoxicity of TIQs is weaker than that of MPTP. Since Parkinson's disease is a slowly progressing neurodegenerative disease, long term neurotoxic effects of IQs remain to be further examined in primates. (C) 1997 Elsevier Science Ireland Ltd.

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Documento generato il 05/07/20 alle ore 09:29:31