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Titolo:
Cell death of dopamine neurons in aging and Parkinson's disease
Autore:
Naoi, M; Maruyama, W;
Indirizzi:
Inst Appl Biochem, Dept Brain Sci, Mitake, Tokyo 506116, Japan Inst Appl Biochem Mitake Tokyo Japan 506116 , Mitake, Tokyo 506116, Japan Natl Inst Longev Sci, Dept Basic Gerontol, Biochem & Metab Lab, Obu, Aichi, Japan Natl Inst Longev Sci Obu Aichi Japan chem & Metab Lab, Obu, Aichi, Japan
Titolo Testata:
MECHANISMS OF AGEING AND DEVELOPMENT
fascicolo: 2-3, volume: 111, anno: 1999,
pagine: 175 - 188
SICI:
0047-6374(19991130)111:2-3<175:CDODNI>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEUROBLASTOMA SH-SY5Y CELLS; N-METHYLTRANSFERASE ACTIVITY; SUBSTANTIA-NIGRA; 1,2(N)-DIMETHYL-6,7-DIHYDROXYISOQUINOLINIUM ION; HUMAN BRAIN; DNA-DAMAGE; RAT-BRAIN; NEUROTOXIN; N-METHYL(R)SALSOLINOL; 1(R),2(N)-DIMETHYL-6,7-DIHYDROXY-1,2,3,4-TETRAHYDROISOQUINOLINE;
Keywords:
aging; Parkinson's disease; N-methyl(R)salsolinol; (R)salsolinol N-methyltransferase; oxidative stress;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Naoi, M Inst Appl Biochem, Dept Brain Sci, Yagi Mem Pk, Mitake, Tokyo 506116, Japan Inst Appl Biochem Yagi Mem Pk Mitake Tokyo Japan 506116 116, Japan
Citazione:
M. Naoi e W. Maruyama, "Cell death of dopamine neurons in aging and Parkinson's disease", MECH AGE D, 111(2-3), 1999, pp. 175-188

Abstract

Dopamine neurons in the substantia nigra of human brain are selectively vulnerable and the number decline by aging at 5-10% per decade. Enzymatic andnon-enzymatic oxidation of dopamine generates reactive oxygen species, which induces apoptotic cell death in dopamine neurons. Parkinson's disease (PD) is also caused by selective cell death of dopamine neurons in this brainregion. The pathogenesis of Parkinson's disease remains to be an enigma, but it was found that an endogenous MPTP-like neurotoxin, 1(R), 2(N)dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [N-methyl(R)salsolinol, NM(R)Sal], may be one of the pathogenic agents of PD. NM(R)Sal increases in cerebrospinal fluid from untreated parkinsonian patients, and two enzymes, a (R)salsolinol synthase and a neutral N-methyltransferase, synthesize this neurotoxin in the nigro-striatum. The activity of a neutral N-methyltransferase is significantly higher in lymphocytes from parkinsonian patients than incontrol. The mechanism of cell death by this toxin was proved to be by theinduction of apoptosis, by use of dopaminergic SH-SY5Y cells. The apoptosis was suppressed by anti-oxidants, suggesting that the generation of reactive oxygen species may initiate cellular death process. These results indicate that in aging and PD oxidative stress induces degeneration of dopamine neurons, and the antioxidant therapy may delay the decline of dopamine neurons in the brain. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/07/20 alle ore 06:39:18