Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
THE ROLES OF NEUROMELANIN, BINDING OF METAL-IONS, AND OXIDATIVE CYTOTOXICITY IN THE PATHOGENESIS OF PARKINSONS-DISEASE - A HYPOTHESIS
Autore:
ENOCHS WS; SARNA T; ZECCA L; RILEY PA; SWARTZ HM;
Indirizzi:
7252 STRASENBURGH HALL,RM 308 HANOVER NH 03755 UNIV ILLINOIS,COLL MED URBANA IL 61801 MASSACHUSETTS GEN HOSP,DEPT RADIOL BOSTON MA 02114 HARVARD UNIV,SCH MED BOSTON MA 00000 JAGIELLONIAN UNIV KRAKOW POLAND CNR,IST TECNOL BIOMED AVANZATE I-20131 MILAN ITALY UNIV LONDON LONDON ENGLAND DARTMOUTH COLL SCH MED HANOVER NH 00000
Titolo Testata:
Journal of neural transmission. Parkinson's disease and dementia section
fascicolo: 2, volume: 7, anno: 1994,
pagine: 83 - 100
SICI:
0936-3076(1994)7:2<83:TRONBO>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
ELECTRON-SPIN-RESONANCE; MPTP-INDUCED NEUROTOXICITY; PIGMENTED NERVE-CELLS; X-RAY-MICROANALYSIS; SUBSTANTIA-NIGRA; HYDROGEN-PEROXIDE; SULFHYDRYL COMPOUNDS; FREE-RADICALS; HUMAN-BRAIN; TRANSITION-METALS;
Keywords:
NEUROMELANIN; MELANINS; METAL IONS; FREE RADICALS; OXYGEN TOXICITY; SUBSTANTIA NIGRA; AGING; PARKINSONS DISEASE; IDIOPATHIC PARALYSIS AGITANS;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
151
Recensione:
Indirizzi per estratti:
Citazione:
W.S. Enochs et al., "THE ROLES OF NEUROMELANIN, BINDING OF METAL-IONS, AND OXIDATIVE CYTOTOXICITY IN THE PATHOGENESIS OF PARKINSONS-DISEASE - A HYPOTHESIS", Journal of neural transmission. Parkinson's disease and dementia section, 7(2), 1994, pp. 83-100

Abstract

A characteristic feature of both Parkinson's disease (idiopathic paralysis agitans) and normal aging is loss of pigmented neurons in the substantia nigra. This has been found to correlate with the accumulationof neuromelanin and with oxidative stress in this brain region, but aclear association between these factors has not been established. Based on our recent demonstration that neuromelanin is a true melanin, containing bound metal ions in situ, we present a general model for its accumulation in vivo and the hypotheses (1) that it has a cytoprotective function in the sequestration of redox-active metal ions under normal conditions but (2) that it has a cytotoxic role in the pathogenesisof Parkinson's disease. Thus, neuromelanin accumulates normally through the autooxidation of catecholamines and serves tightly to bind redox-active metal ions, processes which would accelerate under conditionsof intracellular or extracellular oxidative stress. Based on the known properties of melanin, however, neuromelanin also has the potential for exacerbating oxidative stress, eg by generating H2O2 when it is intact or by releasing redox-active metal ions if it loses its integrity; these reactions also would modulate the reactivity of the neuromelanin. By overwhelming intracellular antioxidative defense mechanisms, such a positive-feedback cycle could turn a condition of chronic or repeated oxidative stress in vulnerable neurons into an acute crisis, leading to cellular death. If the cumulative stress in duration and/or degree is severe enough, neuronal depletion could be sufficient to cause Parkinson's disease during life. One possible trigger for this cascadeis suggested by the increased nigral iron contents in postmortem parkinsonian brains and the correlation of this disease with urban living where exposure to heavy metal ions is high: the saturation of neuromelanin with redox-active metal ions. Parkinson's disease therefore may be a form of accelerated aging in the substantia nigra associated with environmental toxins in which neuromelanin has a central, active role.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/07/20 alle ore 14:48:39