title: Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson's disease.
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.
authors.affiliation: Institute of Biomedical Technologies, National Research Council of Italy, Segrate, Milan, Italy.
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Zucca
authors.affiliation: Faculty of Medicine, Molecular and Clinical Pharmacology, ICBM, University of Chile, Santiago, Chile.
authors.forename: Juan
authors.initials: J
authors.lastname: Segura-Aguilar
authors.affiliation: Institute of Biomedical Technologies, National Research Council of Italy, Segrate, Milan, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Ferrari
authors.affiliation: Faculty of Medicine, Molecular and Clinical Pharmacology, ICBM, University of Chile, Santiago, Chile.
authors.forename: Patricia
authors.initials: P
authors.lastname: Muñoz
authors.affiliation: Faculty of Medicine, Molecular and Clinical Pharmacology, ICBM, University of Chile, Santiago, Chile; Department of Basic Sciences, Faculty of Sciences, Santo Tomás University, Viña del Mar, Chile.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Paris
authors.affiliation: Department of Psychiatry, Columbia University Medical Center, New York, NY, USA; Department of Neurology, Columbia University Medical Center, New York, NY, USA; Department of Pharmacology, Columbia University Medical Center, New York, NY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sulzer
authors.affiliation: Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Sarna
authors.affiliation: Department of Chemistry, University of Pavia, Pavia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Casella
authors.affiliation: Institute of Biomedical Technologies, National Research Council of Italy, Segrate, Milan, Italy. Electronic address: luigi.zecca@itb.cnr.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Zecca
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*
chemical_list: D008543:Melanins; C014121:neuromelanin; D007501:Iron; D004298:Dopamine
keywords: Dopamine; Human neuromelanin; Iron; Melanin; Parkinson's disease