Dopaminforschung heute und morgen — L-Dopa in der Zukunft

Riederer, Peter; Sofić, E.; Rausch, Wolf‐Dieter; Kruzik, P.; Youdim, Moussa B. H.

doi:10.1007/978-3-7091-8822-4_14

Cited by 23 publications

(6 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Earlier reports indicated that brain peroxidase and catalase activities were lowered in PD (Ambani et al, 1975). Lowered glutathione (Perry et al, 1982;Riederer et al, 1985) and glutathione per-oxidase (Kish et al, 1985) have led Perry et a]. (1 982) to suggest that PD may be a disorder due to nigral glutathione deficiency.…”

Section: Discussionmentioning

confidence: 99%

Transition Metals, Ferritin, Glutathione, and Ascorbic Acid in Parkinsonian Brains

Riederer

Sofić

Rausch

et al. 1989

Journal of Neurochemistry

1,299

702

View full text Add to dashboard Cite

The regional distributions of iron, copper, zinc, magnesium, and calcium in parkinsonian brains were compared with those of matched controls. In mild Parkinson's disease (PD), there were no significant differences in the content of total iron between the two groups, whereas there was a significant increase in total iron and iron (III) in substantia nigra of severely affected patients. Although marked regional distributions of iron, magnesium, and calcium were present, there were no changes in magnesium, calcium, and copper in various brain areas of PD. The most notable finding was a shift in the iron (II)/iron (III) ratio in favor of iron (III) in substantia nigra and a significant increase in the iron (III)-binding, protein, ferritin. A significantly lower glutathione content was present in pooled samples of putamen, globus pallidus, substantia nigra, nucleus basalis of Meynert, amygdaloid nucleus, and frontal cortex of PD brains with severe damage to substantia nigra, whereas no significant changes were observed in clinicopathologically mild forms of PD. In all these regions, except the amygdaloid nucleus, ascorbic acid was not decreased. 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.

show abstract

Section: Discussionmentioning

confidence: 99%

Transition Metals, Ferritin, Glutathione, and Ascorbic Acid in Parkinsonian Brains

Riederer

Sofić

Rausch

et al. 1989

Journal of Neurochemistry

1,299

702

View full text Add to dashboard Cite

show abstract

Section: Iron In Neurodegenerative Disorders: Parkinson’s Diseasementioning

confidence: 99%

“…1924). Subsequent studies employing different techniques demonstrated an increase in total iron and non‐heme ferric iron (Fe 3+ ) in SN (Earle 1968; Riederer et al. 1985; Dexter et al.…”

Section: Iron In Neurodegenerative Disorders: Parkinson’s Diseasementioning

confidence: 99%

“…Changes in iron content (Table 3) in the basal ganglia (globus pallidus) in PD were first demonstrated in 1924 (Lhermitte et al 1924). Subsequent studies employing different techniques demonstrated an increase in total iron and non-heme ferric iron (Fe 3+ ) in SN (Earle 1968;Riederer et al 1985;Dexter et al 1991). These findings were further endorsed by histopathological and in vivo brain imaging techniques.…”

mentioning

confidence: 99%

“…Genetic mutation(s) may alter the expression and thus function of proteins involved in iron homeostasis and /or its metabolism resulting in its abnormal accumulation in the brain. Changes in brain iron and the iron storage protein ferritin have been found in a prevalent motor disease, Parkinson's disease (PD) (Riederer et al 1985;Dexter et al 1987). The presence of iron deposition and increased free iron concentration in the basal ganglia appears to play a pivotal role in the manifestation of Parkinsonianlike features or Parkinsonism caused by dopamine deficiency.…”

mentioning

confidence: 99%

See 2 more Smart Citations

The relevance of iron in the pathogenesis of Parkinson’s disease

Sian-Hülsmann

Mandel²,

Youdim

et al. 2011

Journal of Neurochemistry

311

214

View full text Add to dashboard Cite

J. Neurochem. (2011) 118, 939–957. Abstract Alterations of iron levels in the brain has been observed and documented in a number of neurodegenerative disorders including Parkinson’s disease (PD). The elevated nigral iron levels observed in PD may reflect a dysfunction of brain iron homeostasis. Under normal physiological conditions excess iron can be sequestrated in ferritin and neuromelanin. Alternatively, the excess iron may represent a component of brain iron deposition associated with ageing. The aetiology of idiopathic PD largely remains an enigma. However, intensive investigations have provided a host of putative mechanisms that might contribute to the pathogenesis underlying the characteristic degeneration of the dopaminergic neurons in the substantia nigra (SN). The mechanisms proposed include oxidative (and nitrative) stress, inflammation, excitotoxicity, mitochondrial dysfunction, altered proteolysis and finally apoptotic induced cell death. Iron‐mediated cellular destruction is mediated primarily via reactive oxygen or/and nitrogen species induced oxidative stress. Furthermore, these pathogenic mechanisms appear to be closely interlinked to the cascade of events leading to cellular death. There are conflicting reports about the stage during disease progression at which nigral iron change occurs in PD. Some have found that there are no changes in iron content SN in asymptomatic incidental Lewy body disease, suggesting it may represent a secondary event in the cascade of neuronal degeneration. In contrast, others have found an elevation of iron in SN in pre‐clinical stages. These discrepancies may be attributed to the occurrence of different sub‐groups of the disease. This concurs with the notion that PD represents a group of related diseases with a number of potential pathogenic pathways.

show abstract

The possible role of iron in the etiopathology of parkinson's disease

1993

Self Cite

View full text Add to dashboard Cite

The identification of 6-hydroxydopamine (6-OHDA) and N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as dopaminergic neurotoxins that can induce parkinsonism in humans and animals has contributed to a better understanding of Parkinson's disease (PD). Although the involvement of similar neurotoxins has been implicated in PD, the etiology of the disease remains obscure. However, the recently described pathology of PD supports the view for a state of oxidative stress in the substantia nigra (SN), resulting as a consequence of the selective accumulation of iron in SN zona compacta and within the melanized dopamine neurons. Whether iron is directly involved cannot be ascertained. Nevertheless, the biochemical changes due to oxidative stress resulting from tissue iron overload (siderosis) are similar to those now being identified in parkinsonian SN. These include the reduction of mitochondrial electron transport, complex I and III activities, glutathione peroxidase activity, glutathione (GSH) ascorbate, calcium-binding protein, and superoxide dismutase and increase of basal lipid peroxidation and deposition of iron. The participation of iron-induced oxygen free radicals in the process of nigrostriatal dopamine neuron degeneration is strengthened by recent studies in which the neurotoxicity of 6-OHDA has been linked to the release of iron from its binding sites in ferritin. This is further supported by experiments with the prototype iron chelator, desferrioxamine (Desferal), a free-radical inhibitor, which protects against 6-OHDA-induced lesions in the rat. Indeed, intranigral iron injection in rats produces a selective lesioning of dopamine neurons, resulting in a behavioral and biochemical parkinsonism.

show abstract

Dopaminforschung heute und morgen — L-Dopa in der Zukunft

Cited by 23 publications

References 37 publications

Transition Metals, Ferritin, Glutathione, and Ascorbic Acid in Parkinsonian Brains

Transition Metals, Ferritin, Glutathione, and Ascorbic Acid in Parkinsonian Brains

The relevance of iron in the pathogenesis of Parkinson’s disease

The possible role of iron in the etiopathology of parkinson's disease

Contact Info

Product

Resources

About