Journal ArticleDOI
Absence of mutations in superoxide dismutase and catalase genes in patients with Parkinson's disease
J. S. Parboosingh,M. Rousseau,F. Rogan,Z. Amit,H. Chertkow,W. G. Johnson,F. Manganaro,H. N. Schipper,T. J. Curran,J. Stoessl,Guy A. Rouleau +10 more
TLDR
Parkinson's disease is not caused by mutations in the genes of these three detoxifying enzymes, and the exon 9 variant in the catalase gene in the one family with PD is most likely a silent mutation and not the genetic cause of PD in this family.Abstract:
Background: Parkinson's disease (PD) is an adultonset, neurodegenerative disorder characterized by a selective loss of the dopaminergic cells of the substantia nigra and by progressive motor decline. Studies have shown aberrant oxidative stress metabolism within the substantia nigra and other dopaminergic regions of the brain in patients with PD. Objective: To screen the genes of three free radical detoxifying enzymes—copper/zinc superoxide dismutase, manganese superoxide dismutase, and catalase—for mutations in patients with PD. Patients and Methods: A total of 107 unrelated patients with PD from two PD populations (familial and sporadic) were screened for mutations in the genes of copper/zinc superoxide dismutase, manganese superoxide dismutase, and catalase by single-strand conformation analysis. The diagnosis of PD was based on the clinical observations of resting tremor, rigidity, and bradykinesia. Results: No mutations were identified. However, we did identify an amino acid substitution (glycine to aspartic acid) in exon 9 of the catalase gene in one patient; decreased red blood cell catalase activity was observed in this patient. Conclusion: Parkinson's disease is not caused by mutations in the genes of these three detoxifying enzymes. The exon 9 variant in the catalase gene in the one family with PD is most likely a silent mutation and not the genetic cause of PD in this family.read more
Citations
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Journal ArticleDOI
Neuroprotective strategies in Parkinson's disease : an update on progress.
TL;DR: In spite of the extensive studies performed on postmortem substantia nigra from Parkinson’s disease patients, these studies have demonstrated that, at the time of death, a cascade of events had been initiated that may contribute to the demise of the melanin-containing nigro-striatal dopamine neurons.
Journal ArticleDOI
Cu/Zn superoxide dismutase gene mutations in amyotrophic lateral sclerosis: correlation between genotype and clinical features.
A Radunovíc,P N Leigh +1 more
TL;DR: Investigations in Australia, subsequent to the publication of the paper by Cleveland et al ,2identified the mutation in this family as His43Arg, not Gly37Arg, and the mutation was identified as H43R by investigations in Australia.
Journal ArticleDOI
Genes and parkinsonism.
TL;DR: The molecular genetics of Parkinson's disease as currently understood is described to help explain the pathways that underlie neurodegeneration.
Journal ArticleDOI
Peroxisomal Hydrogen Peroxide Metabolism and Signaling in Health and Disease
TL;DR: The focus of this review is to comprehensively evaluate the evidence that peroxisomes, organelles best known for their role in cellular lipid metabolism, also serve as hubs in the H2O2 signaling network.
Journal ArticleDOI
Etiology of Parkinson's Disease
TL;DR: Genetic factors, infectious and immunological abnormalities, the effects of ageing, toxins, toxins (endogenous as well as exogenous) and other environmental factors may all contribute to the development of Parkinson's disease.
References
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Journal ArticleDOI
DNA sequencing with chain-terminating inhibitors
TL;DR: A new method for determining nucleotide sequences in DNA is described, which makes use of the 2',3'-dideoxy and arabinon nucleoside analogues of the normal deoxynucleoside triphosphates, which act as specific chain-terminating inhibitors of DNA polymerase.
Journal ArticleDOI
Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
TL;DR: Tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O–2 to O2 and H2O2 is reported.
Journal ArticleDOI
Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase
Han Xiang Deng,Afif Hentati,John A. Tainer,Zafar Iqbal,Annarueber Cayabyab,Wu Yen Hung,Elizabeth D. Getzoff,Ping Hu,Brian Herzfeldt,Raymond P. Roos,Carolyn Warner,Gang Deng,Edwin Soriano,Celestine Smyth,Hans E. Parge,Aftab Ahmed,Allen D. Roses,Robert A. Hallewell,Margaret A. Pericak-Vance,Teepu Siddique +19 more
TL;DR: In this article, single-site mutants in the Cu,Zn superoxide dismutase (SOD) gene occur in patients with the fatal neurodegenerative disorder familial amyotrophic lateral sclerosis.
Journal ArticleDOI
Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains.
Peter Riederer,Emin Sofic,Wolf-Dieter Rausch,Bruno Schmidt,Gavin P. Reynolds,Kurt A. Jellinger,Moussa B.H. Youdim +6 more
TL;DR: Reduced glutathione and the shift of the iron (II)/iron (III) ratio in favor of iron ( III) suggest that these changes might contribute to pathophysiological processes underlying PD.
Journal ArticleDOI
Basal Lipid Peroxidation in Substantia Nigra Is Increased in Parkinson's Disease
D. Dexter,C.J. Carter,F. R. Wells,F. Javoy-Agid,Yves Agid,Andrew J. Lees,Peter Jenner,C. D. Marsden +7 more
TL;DR: The results may indicate that an increased level of lipid peroxidation continues to occur in the parkinsonian nigra up to the time of death, perhaps because of continued exposure to excess free radicals derived from some endogenous or exogenous neurotoxic species.
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