| Abstract | 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. |
| Text | 284588 2014 10.1007/s12640 013 9435 y ISI Web of Science WOS 000329326600002 PubMed 24155156 neuromelanin substantia nigra Parkinson s disease aging neuroinflammation neurodegeneration Neuromelanin of the Human Substantia Nigra An Update Zucca F.A.; Basso E.; Cupaioli F.A.; Ferrari E.; Sulzer D.; Casella L.; Zecca L. Zucca, Fabio A.; Basso, Emy; Cupaioli, Francesca A.; Ferrari, Emanuele; Zecca, Luigi Institute of Biomedical Technologies, National Research Council of Italy, Via Cervi, 93, 20090 Segrate MI , Italy; Sulzer, David Department of Psychiatry, Neurology and Pharmacology, Columbia University, New York, NY 10032, USA; Casella, Luigi Department of Chemistry, University of Pavia, 27100 Pavia, Italy. Zecca, L reprint author , Institute of Biomedical Technologies, National Research Council of Italy, Via Cervi, 93, 20090 Segrate MI , Italy; e mail luigi.zecca@itb.cnr.it 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. 25 Published version Publication date 2014 Jan. Epub 2013 Oct 24. Articolo in rivista Springer 1029 8428 Neurotoxicity resarch Neurotoxicity resarch Neurotox. res. Neurotoxicity research. Neurotoxicity research Print francescaanna.cupaioli CUPAIOLI FRANCESCA ANNA emanuele.ferrari FERRARI EMANUELE fabioandrea.zucca ZUCCA FABIO ANDREA emy.basso BASSO EMY luigi.zecca ZECCA LUIGI ME.P02.018.001 Invecchiamento e malattie neurodegenerative |
