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Titolo:
MITOCHONDRIA IN THE ETIOLOGY AND PATHOGENESIS OF PARKINSONS-DISEASE
Autore:
SCHAPIRA AHV; GU M; TAANMAN JW; TABRIZI SJ; SEATON T; CLEETER M; COOPER JM;
Indirizzi:
UNIV LONDON,ROYAL FREE HOSP,SCH MED,DEPT CLIN NEUROSCI,ROWLAND HILL ST LONDON NW3 2PF ENGLAND INST NEUROL LONDON WC1N 3BG ENGLAND
Titolo Testata:
Annals of neurology
fascicolo: 3, volume: 44, anno: 1998, supplemento:, 1
pagine: 89 - 98
SICI:
0364-5134(1998)44:3<89:MITEAP>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
COMPLEX-I DEFICIENCY; MAGNETIC-RESONANCE SPECTROSCOPY; NEURONAL NITRIC-OXIDE; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; SUBSTANTIA-NIGRA; SKELETAL-MUSCLE; INHIBITION; BRAIN; NEUROTOXICITY; MUTATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
64
Recensione:
Indirizzi per estratti:
Citazione:
A.H.V. Schapira et al., "MITOCHONDRIA IN THE ETIOLOGY AND PATHOGENESIS OF PARKINSONS-DISEASE", Annals of neurology, 44(3), 1998, pp. 89-98

Abstract

Mitochondria play a critical role in cellular energy metabolism. The identification of a respiratory chain defect in Parkinson's disease (PD) provides not only a direct link with toxin models of parkinsonism but also insight into the mechanisms involved in etiology and pathogenesis. The presence of the complex I deficiency in PD substantia nigra and platelets suggests the involvement of a systemic cause. Genomic transplantation studies have been undertaken that involve the transfer toa novel nuclear background of mitochondrial DNA (mtDNA) from PD patients with a complex I defect, followed by both mixed and clonaI expansion of the resulting cybrids. The mixed cybrids with the PD mtDNA expressed the complex I defect present in the original PD donor platelets. Clonal expansion of one such mixed cybrid culture produced a spectrum of clones with complex I and complex IV activities, ranging from severe deficiency to normal range, a pattern typical of a heteroplasmic mtDNA mutation. Histochemical, immunohistochemical, and functional assessments of Delta psi(m), all showed a pattern in the PD clones typical of that produced by a mtDNA mutation. Patients with focal dystonia and a platelet complex I defect were used as disease controls for the cybrid studies. The mitochondrial abnormality was eradicated by transfer of dystonia mtDNA to a control nuclear background in both mixed and clonal cybrids, with no evidence of clonal heterogeneity. These results help to validate our findings in the PD patients and suggest that the complex I deficiency in dystonia is not due to an abnormality of mtDNA. We hypothesize that the mtDNA defect alone may be the cause of PD in a proportion of patients and may contribute to pathogenesis in others. Identification of the mtDNA genotype responsible for PD may allow thetesting of neuroprotective strategies in appropriate patients.

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Documento generato il 01/04/20 alle ore 21:04:45