Iron as catalyst for oxidative stress in the pathogenesis of Parkinson's disease?

Kienzl, E.; Jellinger, K. A.; Stachelberger, H.; Linert, Wolfgang

doi:10.1016/s0024-3205(99)00458-0

Cited by 60 publications

(34 citation statements)

References 10 publications

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“…24,25 Recent studies suggest that neuromelanin may be a double-edged sword, having the potential to be either cytotoxic or neuroprotective depending upon the cellular environment, such as the concentration of iron and the interactions between dopamine, neuromelanin and iron. 22,23,26,27 DOPA, biosynthesized from tyrosine and as a dopamine precursor, is a major treatment for the symptoms of PD and can synthesize melanin through a complex series of enzymatic and chemical reactions. [28][29][30][31][32][33] It is known that aluminum ions can bind to catechol and o-semiquinone radical centers within melanin polymers to yield chelate complexes, [34][35][36] but the mechanism of enhancement oxidation of catechol by aluminum ions is unclear.…”

Section: Introductionmentioning

confidence: 99%

Aluminum Facilitation of the Iron-Mediated Oxidation of DOPA to Melanin

2004

ANAL. SCI.

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Aluminum, a trivalent cation unable to undergo redox reactions, is shown to faciliate iron-initiated DOPA oxidation in the melanin pathway under acidic condition of pH 5.5, which is a favored medium for aluminum facilitation of iron-induced lipid peroxidation. In the process of oxidation of DOPA to melanin in the presence of the metal ions, Fe 3+ and H2O2 oxidize DOPA to dopachrome (DC), then Al 3+ catalyzes the conversion of DC to 5,6-dihydroxyindole (DHI) and finally Fe 3+ oxidizes DHI to indole-5,6-quinone (IQ), which polymerizes immediately to melanochrome and melanin. The reactions involve the intermediate complexes of metal ions and DOPA or its derivative. The present results indicate that aluminum can enhance the oxidative stress on iron-mediated DOPA oxidation in melanin pathway under acidic condition through the cooperation of iron and aluminum ions.

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Section: Introductionmentioning

confidence: 99%

Aluminum Facilitation of the Iron-Mediated Oxidation of DOPA to Melanin

2004

ANAL. SCI.

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“…The effects of 6-OHDA (SOD), by scavenging superoxide radicals, dramatically inon both the central and peripheral catecholaminergic pathways hibits the oxidation of 6-OHDA (39). Subsequent studies in rodents and in a variety of cultured cell types have been re-have confirmed the production of superoxide radicals, and viewed elsewhere, as well as the molecular basis for its speci-have moreover demonstrated that superoxide radicals generficity (45,46,65). 6-OHDA can be administered to rodents via ated by the first step of 6-OHDA oxidation are critical in a variety of different routes, but its proper utilization in vivo propagating the oxidation of 6-OHDA (11,30,31,80 This shows that the oxidation of 2 moles of 6-OHDA leads to THE HERBICIDE PARAQUAT the formation of 2 moles of quinone and 2 moles of H,0 2 .…”

Section: Still In the Racementioning

confidence: 91%

“…Still, molecular oxygoal will not be discussed. Readers interested in these latter gen is mandatory for the reaction or, in anaerobic conditions, aspects are encouraged to review other references (65, 66). no conversion of 6-OHDA into quinones is detectable (30).…”

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Role of Inflammation in MPTP-Induced Dopaminergic Degeneration

Przedborski¹

2005

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of Information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302 Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. se. TASK NUMBER 5f. WORK UNIT NUMBER REPORT DATE PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERColumbia University New York, NY 10032 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTESOriginal contains colored plates: ALL DTIC reproductions will be in black and white. ABSTRACTWe are investigating the role of inflammation in the death of the dopamine (DA) neuron in the substantia nigra of MPTPtreated mice. Studies in our model over the course of this program project show that microglia are the source of superoxide and nitric oxide through up-regulation of the microglial enzymes NADPH oxidase and inducible nitric oxide synthase (iNOS). We show that activation of microglia in vivo occurs as early as 24 hours after MPTP administration at which time the presence of superoxide in the SNpc after MPTP is noted using hydroethidium histochemistry. M40401, a nonpeptidyl SOD mimetic with catalytic activity equal to or greater than native MnSOD decreased the presence of superoxide and attenuated microglial activation in the SNpc of our mice. Minocycline, a second generation antibiotic, inhibited iNOS up-regulation and also reduced microglial activation. Further, we demonstrate that cyclooxygenase-2 is a part of the inflammatory response in MPTP-treated mice. Our neuronal/microglial cultures now that they are up and running, should give a more exact timeframe of microglial activation in relation to DA neuron death in the MPTP mouse model of PD. Furthermore, we identify components of microglia that may be therapeutic targets. Parkinson's disease (PD) is a common neurodegenerative disorder characterized behaviorally by resting tremor, rigidity, akinesialbradykinesia and postural instability (Fahn and Przedborski, 2000). Neurons associated with the behavioral component of PD are mainly, though not exclusively, the dopaminergic (DA) ...

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“…17 Recently, the hypothesis based on the increase of concentration of trace metallic elements, especially iron, has achieved special interest as a possible cause of the pathogenesis of the disease. [18][19][20] The presence of high concentration of iron would promote generation of free radicals that cause oxidative stress and neuronal degeneration. 21 …”

Section: Introductionmentioning

confidence: 99%

The Role of Trace Metallic Elements in Neurodegenerative Disorders: Quantitative Analysis Using XRF and XANES Spectroscopy

Ide‐Ektessabi

Rabionet

2005

ANAL. SCI.

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Metallic elements are required in numerous essential biological processes of the human body. Transition metal elements like iron, zinc or copper bound to proteins (metalloproteins) perform a variety of complex biological functions as catalysts which regulate biochemical reactions and physiological functions in cells and organs. Published reports have been pointing out that excessive accumulation or a disequilibrium within the concentrations or distributions of these elements may affect cell functions up to the point of degeneration or cell death. 1 Specifically, imbalances of trace metallic elements may be deeply related to neuronal cell death in several neurodegenerative disorders by promoting oxidative stress. 2,3The aim of our studies have been the investigation of the distribution, concentration and chemical state of trace metallic elements in the cells, in order to understand the role of these elements in neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and Amyotrophic lateral sclerosis. To gain a broader understanding of the underlying behavior of these elements in the neurodegeneration process, samples derived from human, monkey and mouse specimens were studied.For carrying out the analyses of these experiments, X-ray fluorescence spectroscopy (XRF) and X-ray absorption near edge structure spectroscopy (XANES), both using synchrotron radiation (SR) microbeams were applied. Synchrotron radiation is an ideal X-ray source which provides continuous and high intensity photon energy. Wide energy tunability and high brightness and collimation are the main features of SR. This allows the investigation of trace metallic elements with a low detection limit (∼0.1 pg) and high spatial resolution. SR-XRF is used for identifying trace elements, as well as determining their distribution and concentration on a single cell level. On the other side, SR-XANES is sensitive to valence state, local atomic structure and chemical state of the elements of the samples. Futhermore, the non-invasive nature of XRF and XANES techniques allows further examinations of the biological samples a posteriori by complementary methods, e.g. histological observations by staining, rendering procedures like isolating or purifying, basically unnecessary. Excessive Accumulations of Fe, Zn and Cu in the Neurons from an Alzheimer's Disease Patient IntroductionAlzheimer's disease (AD) is a progressive neurodegenerative disorder which gradually affects memory, thinking, communication, emotion and behavior. The pathological features of AD are senile plaques, neurofibrillary tangles, neuropil thread formation and neuron and synapse loss. The cause of this dementia is still not clear but recent investigations suggested that the deposition of amyloid-β (Aβ) peptide, free radical mediated processes and genetic defects like mutations of presenilin contribute to the pathogenesis of AD. These molecules combined with excessive accumulation of metallic elements or possible changes in the chemical state of transition metals like iron, c...

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Iron as catalyst for oxidative stress in the pathogenesis of Parkinson's disease?

Cited by 60 publications

References 10 publications

Aluminum Facilitation of the Iron-Mediated Oxidation of DOPA to Melanin

Aluminum Facilitation of the Iron-Mediated Oxidation of DOPA to Melanin

Role of Inflammation in MPTP-Induced Dopaminergic Degeneration

The Role of Trace Metallic Elements in Neurodegenerative Disorders: Quantitative Analysis Using XRF and XANES Spectroscopy

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