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Role and function of neuromelanin in neuronal degeneration

Abstract
In Parkinson´s disease, dopaminergic cell death is accompanied or preceeded by loss of neuromelanin pigmentation. This led to speculations that neuromelanin (NM) might itself be neurotoxic. On the one hand it has been reported that iron accumulates in the substantia nigra of parkinsonian patients, and it has been suggested that iron becomes a neurotoxic agent when complexed with NM. On the other hand, MPP+ has been found to selectively destroy the catecholaminergic nerve cells in the brain. Therefore we used either Fe3+ -complexed with NM- or MPP+ to enhance neurotoxicity in the dopaminergic cell cultures.
A neurotoxic potential of exogenously added NM was found. Primary cultures of mice dopaminergic cells exposed to NM led to a significant loss in cell number, swelling of neural processes, rounding of cells, and occasional inclusion of NM particles particularly into glial elements. Addition of MPP+ or of Fe3+ into the medium increased toxicity particularly together with the oxidatively damaged NM. Synthetic Neuromelanin, however, could not attenuate their toxic effects and displayed high toxicity to dopaminergic cultures in high concentrations.
Project leader
Rausch Wolf-Dieter
Duration
01.01.00-31.12.01
Type of Research
Basic research
Vetmed Research Units
Institute for Medical Biochemistry
Projekt partner
Julius-Maximilians-Universität Würzburg, Versbacher Straße 7, 97078 Würzburg, Germany
Funded by
Österreichische Akademie der Wissenschaften, Wien, Austria
3 Publications

Zecca, L; Berg, D; Arzberger, T; Ruprecht, P; Rausch, WD; Musicco, M; Tampellini, D; Riederer, P; Gerlach, M; Becker, G (2005): In vivo detection of iron and neuromelanin by transcranial sonography: a new approach for early detection of substantia nigra damage. Mov Disord. 2005; 20(10):1278-1285

Moldzio, R; Nguyen, A; Gille, G; Hung, ST; Rausch, WD (2002): Co-treatment of Fe3+ or MPP+ enhance the neurotoxicity of synthetic neuromelanin on dopaminergic cells. Federation of European Neuroscience Societies - FENS. Abstr. A 186.3--FENS Forum 2002; JUL 13-17, 2002; Paris, France.

Nguyen, A; Gille, G; Moldzio, R; Hung, ST; Rausch, WD (2002): Synthetic neuromelanin is toxic to dopaminergic cell cultures. J Neural Transm. 2002; 109(5-6):651-661

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