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Luigi Zecca - One of the best experts on this subject based on the ideXlab platform.
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Interactions of iron, dopamine and Neuromelanin pathways in brain aging and Parkinson's disease.
Progress in neurobiology, 2015Co-Authors: Fabio A. Zucca, Emanuele Ferrari, David Sulzer, Luigi Casella, Tadeusz Sarna, Juan Segura-aguilar, Patricia Muñoz, Irmgard Paris, Luigi ZeccaAbstract:There are several interrelated mechanisms involving iron, dopamine, and Neuromelanin in neurons. Neuromelanin accumulates during aging and is the catecholamine-derived pigment of the dopamine neurons of the substantia nigra and norepinephrine neurons of the locus coeruleus, the two neuronal populations most targeted in Parkinson's disease. Many cellular redox reactions rely on iron, however an altered distribution of reactive iron is cytotoxic. In fact, increased levels of iron in the brain of Parkinson's disease patients are present. Dopamine accumulation can induce neuronal death; however, excess dopamine can be removed by converting it into a stable compound like Neuromelanin, and this process rescues the cell. Interestingly, the main iron compound in dopamine and norepinephrine neurons is the Neuromelanin-iron complex, since Neuromelanin is an effective metal chelator. Neuromelanin serves to trap iron and provide neuronal protection from oxidative stress. This equilibrium between iron, dopamine, and Neuromelanin is crucial for cell homeostasis and in some cellular circumstances can be disrupted. Indeed, when Neuromelanin-containing organelles accumulate high load of toxins and iron during aging a neurodegenerative process can be triggered. In addition, Neuromelanin released by degenerating neurons activates microglia and the latter cause neurons death with further release of Neuromelanin, then starting a self-propelling mechanism of neuroinflammation and neurodegeneration. Considering the above issues, age-related accumulation of Neuromelanin in dopamine neurons shows an interesting link between aging and neurodegeneration.
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Neuromelanin of the Human Substantia Nigra: An Update
Neurotoxicity Research, 2014Co-Authors: Fabio A. Zucca, Emy Basso, Francesca A. Cupaioli, Emanuele Ferrari, David Sulzer, Luigi Casella, Luigi ZeccaAbstract:Dopaminergic neurons of the substantia nigra selectively degenerate over the course of Parkinson’s disease. These neurons are also the most heavily pigmented cells of the brain, accumulating the dark pigment Neuromelanin over a lifetime. The massive presence of Neuromelanin in these brain areas has long been suspected as a key factor involved in the selective vulnerability of neurons. The high concentration of Neuromelanin in substantia nigra neurons seems to be linked to the presence of considerable amounts of cytosolic dopamine that have not been sequestered into synaptic vesicles. Over the past few years, studies have uncovered a dual nature of Neuromelanin. Intraneuronal Neuromelanin can be a protective factor, shielding the cells from toxic effects of redox active metals, toxins, and excess of cytosolic catecholamines. In contrast, Neuromelanin released by dying neurons can contribute to the activation of neuroglia triggering the neuroinflammation that characterizes Parkinson’s disease. This article reviews recent studies on the molecular aspects of Neuromelanin of the human substantia nigra.
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An XAS study of the sulfur environment in human Neuromelanin and its synthetic analogs
European biophysics journal : EBJ, 2009Co-Authors: Pier Raimondo Crippa, Melvin Eisner, Silvia Morante, Francesco Stellato, Flavio C. Vicentin, Luigi ZeccaAbstract:Neuromelanin is a complex molecule accumulating in the catecholaminergic neurons that undergo a degenerative process in Parkinson’s disease. It has been shown to play either a protective or a toxic role depending on whether it is present in the intraneuronal or extraneuronal milieu. Understanding its structure and synthesis mechanisms is mandatory to clarify the reason for this remarkable dual behavior. In the present study, X-ray absorption spectroscopy is employed to investigate the sulfur binding mode in natural human Neuromelanin, synthetic Neuromelanins, and in certain structurally known model compounds, namely cysteine and decarboxytrichochrome C. Based on comparative fits of human and synthetic Neuromelanin spectra in terms of those of model compounds, the occurrence of both cysteine- and trichochrome-like sulfur coordination modes is recognized, and the relative abundance of these two types of structural arrangement is determined. Data on the amount of cysteine- and trichochrome-like sulfur measured in this way indicate that among the synthetic Neuromelanins those produced by enzymatic oxidation are the most similar ones to natural Neuromelanin. The interest of the method described here lies in the fact that it allows the identification of different sulfur coordination environments in a physically nondestructive way.
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Neuromelanins isolated from different regions of the human brain exhibit a common surface photoionization threshold.
Photochemistry and photobiology, 2008Co-Authors: William D. Bush, Luigi Zecca, Fabio A. Zucca, J.m. Garguilo, Chiara Bellei, Robert Nemanich, Glenn S. Edwards, John D. SimonAbstract:Neuromelanin isolated from the premotor cortex, cerebellum, putamen, globus pallidus and corpus callosum of the human brain is studied by scanning probe and photoelectron emission microscopies and the results are compared with previously published work on Neuromelanin from the substantia nigra. Scanning electron microscopy reveals common structure for all Neuromelanins. All exhibit spherical entities of diameters between 200 and 400 nm, composed of smaller spherical substructures, ∼30 nm in diameter. These features are similar to that observed for many melanin systems including Sepia cuttlefish, bovine eye, and human eye and hair melanosomes. Photoelectron microscopy images were collected for all Neuromelanins at specific wavelengths of ultraviolet light between 248 and 413 nm, using the spontaneous emission output from the Duke free electron laser. Analysis of the data establishes a common threshold photoionization potential for Neuromelanins of 4.7 ± 0.2 eV, corresponding to an oxidation potential of −0.3 ± 0.2 V vs the normal hydrogen electrode (NHE). These results are consistent with previously reported potentials for Neuromelanin from the substantia nigra of 4.5 ± 0.2 eV (−0.1 ± 0.2 V vs NHE). All Neuromelanins exhibit a common low surface oxidation potential, reflecting their eumelanic component and their inability to trigger redox processes with neurotoxic effect.
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New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Luigi Zecca, Luigi Casella, Chiara Bellei, Patrizia Costi, Alberto Albertini, Enrico Monzani, Mario Gallorini, Luigi Bergamaschi, Alberto Moscatelli, Nicholas J. TurroAbstract:Neuronal pigments of melanic type were identified in the putamen, cortex, cerebellum, and other major regions of human brain. These pigments consist of granules 30 nm in size, contained in organelles together with lipid droplets, and they accumulate in aging, reaching concentrations as high as 1.5–2.6 μg/mg tissue in major brain regions. These pigments, which we term Neuromelanins, contain melanic, lipid, and peptide components. The melanic component is aromatic in structure, contains a stable free radical, and is synthesized from the precursor molecule cysteinyl-3,4-dihydroxyphenylalanine. This contrasts with Neuromelanin of the substantia nigra, where the melanic precursor is cysteinyl-dopamine. These neuronal pigments have some structural similarities to the melanin found in skin. The precursors of lipid components of the Neuromelanins are the polyunsaturated lipids present in the surrounding organelles. The synthesis of Neuromelanins in the various regions of the human brain is an important protective process because the melanic component is generated through the removal of reactive/toxic quinones that would otherwise cause neurotoxicity. Furthermore, the resulting melanic component serves an additional protective role through its ability to chelate and accumulate metals, including environmentally toxic metals such as mercury and lead.
Tadeusz Wilczok - One of the best experts on this subject based on the ideXlab platform.
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Pyrolysis-gas chromatography-mass spectrometry of synthetic Neuromelanins
Journal of Analytical and Applied Pyrolysis, 2002Co-Authors: Anna Dzierżęga-lęcznar, Ewa Chodurek, Krystyna Stępień, Tadeusz WilczokAbstract:Abstract Synthetic Neuromelanins obtained from dopamine and/or 5- S -cysteinyldopamine were pyrolyzed at 770 °C. The thermal degradation products were separated by gas chromatography and identified by mass spectrometry. Pyrolytic patterns of melanins containing 5- S -cysteinyldopamine-derived component were different from that of dopamine-melanin. Major pyrolytic products of 5- S -cysteinyldopamine-originated units were indentified as 2H-1,4-benzothiazin-5-one, 4-hydroxybenzothiazole and thiazoloisoquinoline and their alkyl derivatives. The results obtained indicate that pyrolysis-gas chromatography-mass spectrometry method is suitable for identification of 5- S -cysteinyldopamine-derived units in synthetic melanin copolymers and it could be applied for structural analysis of natural Neuromelanin.
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Model Neuromelanins as antioxidative agents during lipid peroxidation.
Neurotoxicity research, 1999Co-Authors: Tadeusz Wilczok, Anna Dzierżęga-lęcznar, Krystyna Stępień, Alicja Zajdel, Adam WilczokAbstract:The oxidative pathway of dopamine metabolism in the human brain leads to formation and accumulation of Neuromelanin in the cytoplasm of most nigrostriatal dopaminergic neurons. The physiological significance of Neuromelanin and its contribution to the neurodegenerative processes underlying Parkinson's disease are still controversial. The effect of model Neuromelanins on Fe(II)/ascorbate-induced lipid peroxidation in micelles of linoleic acid and in lecithin liposomes was determined. Synthetic Neuromelanins were obtained from dopamine (DA), 5-S-cysteinyldopamine (CysDA) or from equimolar mixture of these precursors. Thiobarbituric acid test and reverse-phase HPLC, used for measurements of primary and secondary oxidation products, showed that all melanins tested significantly suppressed peroxidation of both, linoleic acid and liposomal lecithin. The inhibitory effect of CysDA-melanin was lower than of DA/CysDA-melanin and DA-melanin. All the melanins were able to reduce linoleic acid hydroperoxides to their stable hydroxy derivatives. The results obtained suggest that Neuromelanin can act as natural antioxidant. The fatty acid hydroperoxide-reducing ability demonstrated for the model Neuromelanins appears to be involved in the mechanism of antioxidative activity of Neuromelanin.
Peter Riederer - One of the best experts on this subject based on the ideXlab platform.
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Melanin and Neuromelanin Fluorescence Studies Focusing on Parkinson’s Disease and Its Inherent Risk for Melanoma
Cells, 2019Co-Authors: Dieter Leupold, Peter Riederer, Lukasz Szyc, Goran Stankovic, Sabrina Strobel, Hans-ullrich Völker, Ulrike Fleck, Thomas Müller, Matthias Scholz, Camelia-maria MonoranuAbstract:Parkinson’s disease is associated with an increased risk of melanoma (and vice versa). Several hypotheses underline this link, such as pathways affecting both melanin and Neuromelanin. For the first time, the fluorescence of melanin and Neuromelanin is selectively accessible using a new method of nonlinear spectroscopy, based on a stepwise two-photon excitation. Cutaneous pigmentation and postmortem Neuromelanin of Parkinson patients were characterized by fluorescence spectra and compared with controls. Spectral differences could not be documented, implying that there is neither a Parkinson fingerprint in cutaneous melanin spectra nor a melanin-associated fingerprint indicating an increased melanoma risk. Our measurements suggest that Parkinson’s disease occurs without a configuration change of Neuromelanin. However, Parkinson patients displayed the same dermatofluorescence spectroscopic fingerprint of a local malignant transformation as controls. This is the first comparative retrospective fluorescence analysis of cutaneous melanin and postmortem Neuromelanin based on nonlinear spectroscopy in patients with Parkinson’s disease and controls, and this method is a very suitable diagnostic tool for melanoma screening and early detection in Parkinson patients. Our results suggest a non-pigmentary pathway as the main link between Parkinson’s disease and melanoma, and they do not rule out the melanocortin-1-receptor gene as an additional bridge between both diseases.
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Proteomic characterization of Neuromelanin granules isolated from human substantia nigra by laser-microdissection
Scientific Reports, 2016Co-Authors: Sarah Plum, Peter Riederer, Manfred Gerlach, Simone Steinbach, Johannes Attems, Sharon Keers, Katrin MarcusAbstract:Neuromelanin is a complex polymer pigment found primarily in the dopaminergic neurons of human substantia nigra . Neuromelanin pigment is stored in granules including a protein matrix and lipid droplets. Neuromelanin granules are yet only partially characterised regarding their structure and function. To clarify the exact function of Neuromelanin granules in humans, their enrichment and in-depth characterization from human substantia nigra is necessary. Previously published global proteome studies of Neuromelanin granules in human substantia nigra required high tissue amounts. Due to the limited availability of human brain tissue we established a new method based on laser microdissection combined with mass spectrometry for the isolation and analysis of Neuromelanin granules. With this method it is possible for the first time to isolate a sufficient amount of Neuromelanin granules for global proteomics analysis from ten 10 μm tissue sections. In total 1,000 proteins were identified associated with Neuromelanin granules. More than 68% of those proteins were also identified in previously performed studies. Our results confirm and further extend previously described findings, supporting the connection of Neuromelanin granules to iron homeostasis and lysosomes or endosomes. Hence, this method is suitable for the donor specific enrichment and proteomic analysis of Neuromelanin granules.
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Combined enrichment of Neuromelanin granules and synaptosomes from human substantia nigra pars compacta tissue for proteomic analysis
Journal of Proteomics, 2013Co-Authors: Sarah Plum, Carsten Theiss, Renata Leite, Wilson Jacob-filho, Katja Kuhlmann, Stefan Helling, Helmut E. Meyer, Martin Eisenacher, Peter RiedererAbstract:Abstract This article gives a detailed description of a protocol using density gradient centrifugation for the enrichment of Neuromelanin granules and synaptosomes from low amounts (≥ 0.15 g) of human substantia nigra pars compacta tissue. This has a great advantage compared to already existing methods as it allows for the first time (i) a combined enrichment of Neuromelanin granules and synaptosomes and (ii) just minimal amounts of tissue necessary to enable donor specific analysis. Individual specimens were classified as control or diseased according to clinical evaluation and neuropathological examination. For the enrichment of synaptosomes and Neuromelanin granules from the same tissue sample density gradient centrifugations using Percoll® and Iodixanol were performed. The purity of resulting fractions was checked by transmission electron microscopy. We were able to establish a reproducible and easy to handle protocol combining two different density gradient centrifugations: using an Iodixanol gradient Neuromelanin granules were enriched and in parallel, from the same sample, a fraction of synaptosomes with high purity using a Percoll® gradient was obtained. Our subfractionation strategy will enable a subsequent in depth proteomic characterization of neurodegenerative processes in the substantia nigra pars compacta in patients with Parkinson's disease and dementia with Lewy bodies compared to appropriate controls. Biological significance Key features of Parkinson's disease are the degeneration of dopaminergic neurons in the substantia nigra pars compacta, an associated loss of the brain pigment Neuromelanin and a resulting impairment of the neuronal network. The accumulation of iron binding Neuromelanin granules is age- and disease-dependent and disease specific alterations could affect the neuronal iron homeostasis leading to oxidative stress induced cell death. The focus of the described method is the analysis of Neuromelanin granules as well as axonal cell-endings of nerve cells (synaptosomes) of individual donors (control and diseased). It is the basis for the identification of disease-relevant changes in the iron homeostasis and the generation of new insight into altered protein compositions or regulations which might lead to disturbed communications between nerve cells resulting in pathogenic processes.
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Dolichol is the major lipid component of human substantia nigra Neuromelanin
Journal of neurochemistry, 2005Co-Authors: H. Fedorow, Peter Riederer, Glenda M. Halliday, Manfred Gerlach, Kay L. Double, Russell Pickford, James M. Hook, Brett GarnerAbstract:Neuromelanin is a dark brown pigment present at high concentrations in dopaminergic neurones of the human substantia nigra (SN). Early electron microscopic examinations of Neuromelanin fine structure revealed a significant neutral lipid component; however, the identity of this lipid has remained unknown. Here we show that the lipid component of Neuromelanin pigment derived from human SN is the polyisoprenoid dolichol. Established methods were used to isolate the pigment from the SN of 32 brains and the lipid fraction was recovered in high purity and yield. Using reversed-phase HPLC, atmospheric pressure chemical ionization mass spectrometry, and 1 H- and 13 C-NMR techniques, we showed that the Neuromelanin dolichol contained 17‐23 isoprenoid units. Dolichol accounted for 14% of the mass of Neuromelanin pigment; low levels of other hydrophobic compounds were detected (e.g. ubiquinone-10, a-tocopherol and cholesterol together accounted for < 0.5% of the Neuromelanin lipid mass). This is the first time that dolichol has been identified in such a physiological setting and significantly advances our understanding of Neuromelanin pigment structure and biosynthetic pathways. Furthermore, these studies identify a potential novel role for the isoprenoid pathway in the regulation of Neuromelanin function and neurodegeneration within the SN.
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Mössbauer spectroscopic studies of purified human Neuromelanin isolated from the substantia nigra.
Journal of neurochemistry, 2002Co-Authors: Manfred Gerlach, Moussa B. H. Youdim, Luigi Zecca, Alfred X. Trautwein, Peter RiedererAbstract:Abstract:57Fe Mossbauer spectroscopy at different temperatures has been used to characterize the nature of purified human Neuromelanin isolated from the substantia nigra. The quantitative determination of iron(III) by estimation of the overall area of the Mossbauer spectrum at room temperature reveals an iron content of 2.8 ± 1.4%. No subspectra corresponding to divalent iron could be observed in these spectra. The derived Mossbauer parameters lead to the conclusion that the iron sites in the human Neuromelanin are similar to those of human hemosiderin (or ferritin). However, owing to the water insolubility of the purified Neuromelanin, it must be concluded that the Neuromelanin hemosiderin (or ferritin) is bound in a protein matrix that makes it insoluble and difficult to stain histochemically. This protein attachment to Neuromelanin is important in that it is what makes it different from synthetic dopamine melanin.
Sofia Reimão - One of the best experts on this subject based on the ideXlab platform.
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magnetic resonance correlation of iron content with Neuromelanin in the substantia nigra of early stage parkinson s disease
European Journal of Neurology, 2016Co-Authors: Sofia Reimão, P. Pita Lobo, Dulce Neutel, Daisy Abreu, Nilza Gonçalves, Simone Bacellar Leal Ferreira, Rita G. Nunes, Jorge Campos, Joaquim J. FerreiraAbstract:Background and purpose Magnetic resonance (MR) studies have demonstrated a significant reduction of Neuromelanin in the substantia nigra (SN) of Parkinson's disease (PD) patients with high accuracy for differential diagnosis compared to non-PD controls and essential tremor. However, studies state that not knowing how paramagnetic effects of iron influence Neuromelanin signal is a limitation. In this study a Neuromelanin-sensitive MR sequence was combined with T2* relaxometry iron quantification analysis to study the SN of early-stage PD patients to investigate the correlation between these parameters. Methods The inclusion criteria were untreated de novo PD patients and a 2–5 year disease duration (early PD); in addition, age-matched controls were enrolled. These were studied at 3.0 T with a high-resolution T1-weighted MR sequence to visualize Neuromelanin and a relaxometry sequence for iron quantification. The primary outcome was the correlation of the width of the Neuromelanin high signal region and the T2* values in the lateral, central and medial segments of the SN. Results Very weak correlations of T2* values with Neuromelanin width, positive for global and negative for the medial and lateral SN segments, were found in both PD groups and control subjects. The SN Neuromelanin width was markedly reduced in the de novo and early PD groups compared with controls in all SN segments, but no significant difference in T2* values was found between the groups. Conclusions The SN Neuromelanin signal does not have a significant correlation with iron content in PD patients or controls. The Neuromelanin MR signal reduction in PD does not seem to be significantly influenced by paramagnetic iron effects.
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Magnetic resonance correlation of iron content with Neuromelanin in the substantia nigra of early‐stage Parkinson's disease
European journal of neurology, 2015Co-Authors: Sofia Reimão, P. Pita Lobo, Dulce Neutel, Daisy Abreu, Nilza Gonçalves, Simone Bacellar Leal Ferreira, Rita G. Nunes, Jorge Campos, Joaquim J. FerreiraAbstract:Background and purpose Magnetic resonance (MR) studies have demonstrated a significant reduction of Neuromelanin in the substantia nigra (SN) of Parkinson's disease (PD) patients with high accuracy for differential diagnosis compared to non-PD controls and essential tremor. However, studies state that not knowing how paramagnetic effects of iron influence Neuromelanin signal is a limitation. In this study a Neuromelanin-sensitive MR sequence was combined with T2* relaxometry iron quantification analysis to study the SN of early-stage PD patients to investigate the correlation between these parameters. Methods The inclusion criteria were untreated de novo PD patients and a 2–5 year disease duration (early PD); in addition, age-matched controls were enrolled. These were studied at 3.0 T with a high-resolution T1-weighted MR sequence to visualize Neuromelanin and a relaxometry sequence for iron quantification. The primary outcome was the correlation of the width of the Neuromelanin high signal region and the T2* values in the lateral, central and medial segments of the SN. Results Very weak correlations of T2* values with Neuromelanin width, positive for global and negative for the medial and lateral SN segments, were found in both PD groups and control subjects. The SN Neuromelanin width was markedly reduced in the de novo and early PD groups compared with controls in all SN segments, but no significant difference in T2* values was found between the groups. Conclusions The SN Neuromelanin signal does not have a significant correlation with iron content in PD patients or controls. The Neuromelanin MR signal reduction in PD does not seem to be significantly influenced by paramagnetic iron effects.
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Quantitative Analysis Versus Visual Assessment of Neuromelanin MR Imaging for the Diagnosis of Parkinson's disease
Journal of Parkinson's disease, 2015Co-Authors: Sofia Reimão, Dulce Neutel, Miguel Coelho, Mário M. Rosa, Daisy Abreu, Nilza Gonçalves, Patrícia Pita Lobo, Leonor Correia Guedes, Joana Ferreira, C. MorgadoAbstract:Background: Specific MR sequences have been able to identify the loss of Neuromelanin in the substantia nigra (SN) of early stage Parkinson’s disease (PD) patients. Since this technique may have a significant impact in clinical patient management, easy and widely available imaging analysis is needed for routine use. Objective: In this study we compared a quantitative analysis with a visual assessment of SN Neuromelanin-sensitive MR images in early stage PD patients, in terms of pattern changes recognition and diagnostic accuracy. Methods: The inclusion criteria were untreated “de novo” PD patients or a 2–5 year PD duration; in addition, age matched controls were enrolled. These were studied with a high-resolution T1-weighted MR imaging sequence at 3.0 Tesla to visualize Neuromelanin. The primary outcome was the comparison of quantitative width measurement with visual assessment by experienced neuroradiologists of SN Neuromelanin sensitive MR images for PD diagnosis. Results: A total of 12 “de novo” PD patients, 10 PD patients with 2–5 year disease duration and 10 healthy controls were evaluated. We obtained a good accuracy in discriminating early-stage PD patients from controls using either a quantitative width measurement of the T1 high signal or a simple visual image inspection of the SN region. Conclusions: Visual inspection of Neuromelanin-sensitive MR images by experienced neuroradiologists provides comparable results to quantitative width measurement in the detection of early stage PD SN changes and may become a useful tool in clinical practice.
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Substantia nigra Neuromelanin magnetic resonance imaging in de novo Parkinson's disease patients.
European journal of neurology, 2014Co-Authors: Sofia Reimão, P. Pita Lobo, Dulce Neutel, L. Correia Guedes, Miguel Coelho, Mário M. Rosa, Jorge Ferreira, Daisy Abreu, Nilza Gonçalves, C. MorgadoAbstract:Background Depigmentation of the substantia nigra (SN) and locus coeruleus (LC) is a conspicuous pathological feature of Parkinson's disease (PD) and is related to the loss of Neuromelanin, whose paramagnetic properties result in high signal on specific T1-weighted magnetic resonance imaging (MRI). Recent studies have suggested that Neuromelanin decrease in the SN and LC of PD patients may emerge as a possible diagnostic biomarker. The SN Neuromelanin signal in de novo and early stage PD patients was studied to assess its diagnostic accuracy. This is the first study based on a semi-automated MRI analysis of the Neuromelanin signal in de novo PD patients. Methods The inclusion criteria were untreated de novo PD and a 2–5 year disease duration; in addition, age matched healthy controls were enrolled. These were studied with a high-resolution T1-weighted MRI sequence at 3 T to visualize Neuromelanin. The primary outcome was SN high signal area, length and Neuromelanin/midbrain ratio obtained with semi-automated methods. Results A total of 12 de novo PD patients and 10 PD patients with a 2–5 year disease duration were evaluated. The area, length of the SN T1 high signal and the SN Neuromelanin/midbrain ratio were markedly decreased in the PD groups compared with age-matched controls, with a substantial overlap between the two PD groups. Conclusions Neuromelanin-sensitive MRI techniques can discriminate PD patients from healthy individuals with high sensitivity and specificity. Our findings are consistent with recent findings showing that PD Neuromelanin changes remain stable during the course of the disease.
Anna Dzierżęga-lęcznar - One of the best experts on this subject based on the ideXlab platform.
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Pyrolysis-gas chromatography-mass spectrometry of synthetic Neuromelanins
Journal of Analytical and Applied Pyrolysis, 2002Co-Authors: Anna Dzierżęga-lęcznar, Ewa Chodurek, Krystyna Stępień, Tadeusz WilczokAbstract:Abstract Synthetic Neuromelanins obtained from dopamine and/or 5- S -cysteinyldopamine were pyrolyzed at 770 °C. The thermal degradation products were separated by gas chromatography and identified by mass spectrometry. Pyrolytic patterns of melanins containing 5- S -cysteinyldopamine-derived component were different from that of dopamine-melanin. Major pyrolytic products of 5- S -cysteinyldopamine-originated units were indentified as 2H-1,4-benzothiazin-5-one, 4-hydroxybenzothiazole and thiazoloisoquinoline and their alkyl derivatives. The results obtained indicate that pyrolysis-gas chromatography-mass spectrometry method is suitable for identification of 5- S -cysteinyldopamine-derived units in synthetic melanin copolymers and it could be applied for structural analysis of natural Neuromelanin.
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Model Neuromelanins as antioxidative agents during lipid peroxidation.
Neurotoxicity research, 1999Co-Authors: Tadeusz Wilczok, Anna Dzierżęga-lęcznar, Krystyna Stępień, Alicja Zajdel, Adam WilczokAbstract:The oxidative pathway of dopamine metabolism in the human brain leads to formation and accumulation of Neuromelanin in the cytoplasm of most nigrostriatal dopaminergic neurons. The physiological significance of Neuromelanin and its contribution to the neurodegenerative processes underlying Parkinson's disease are still controversial. The effect of model Neuromelanins on Fe(II)/ascorbate-induced lipid peroxidation in micelles of linoleic acid and in lecithin liposomes was determined. Synthetic Neuromelanins were obtained from dopamine (DA), 5-S-cysteinyldopamine (CysDA) or from equimolar mixture of these precursors. Thiobarbituric acid test and reverse-phase HPLC, used for measurements of primary and secondary oxidation products, showed that all melanins tested significantly suppressed peroxidation of both, linoleic acid and liposomal lecithin. The inhibitory effect of CysDA-melanin was lower than of DA/CysDA-melanin and DA-melanin. All the melanins were able to reduce linoleic acid hydroperoxides to their stable hydroxy derivatives. The results obtained suggest that Neuromelanin can act as natural antioxidant. The fatty acid hydroperoxide-reducing ability demonstrated for the model Neuromelanins appears to be involved in the mechanism of antioxidative activity of Neuromelanin.