| Abstract | 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. |
| Text | 339175 2017 10.1016/j.pneurobio.2015.09.012 ISI Web of Science WOS 000403544300007 PubMed 26455458 iron dopamine melanin human neuromelanin Parkinson s disease Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson s disease Zucca F.A.; Segura Aguilar J.; Ferrari E.; Muñoz P.; Paris I.; Sulzer D.; Sarna T.; Casella L.; Zecca L. Zucca, Fabio A.; Ferrari, Emanuele; Zecca, Luigi Institute of Biomedical Technologies, National Research Council of Italy, Segrate, Milan, Italy; Segura Aguilar, Juan; Muñoz, Patricia; Paris, Irmgard Faculty of Medicine, Molecular and Clinical Pharmacology, ICBM, University of Chile, Santiago, Chile; Paris, Irmgard Department of Basic Sciences, Faculty of Sciences, Santo Tomas University, Viña del Mar, Chile; Sulzer, David Department of Psychiatry, Columbia University Medical Center, New York, NY, USA; Sulzer, David Department of Neurology, Columbia University Medical Center, New York, NY, USA; Sulzer, David Department of Pharmacology, Columbia University Medical Center, New York, NY, USA; Sarna, Tadeusz Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland; Casella, Luigi Department of Chemistry, University of Pavia, Pavia, Italy. Zecca, L reprint author , Institute of Biomedical Technologies, National Research Council of Italy, Via Cervi, 93, 20090 Segrate, Milano, Italy; e mail address luigi.zecca@itb.cnr.it 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. 155 Published version Publication date 2017 Aug. Epub 2015 Oct 9. Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson s disease Zucca et al. Prog Neurobiol 2017 PMC.pdf Articolo in rivista Vieweg Sohn. 0301 0082 Progress in neurobiology Print Progress in neurobiology Print Prog. neurobiol. Print Progress in neurobiology. Print emanuele.ferrari FERRARI EMANUELE luigi.zecca ZECCA LUIGI fabioandrea.zucca ZUCCA FABIO ANDREA ME.P02.018.001 Invecchiamento e malattie neurodegenerative |
