期刊
PROGRESS IN NEUROBIOLOGY
卷 155, 期 -, 页码 96-119出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pneurobio.2015.09.012
关键词
Iron; Dopamine; Melanin; Human neuromelanin; Parkinson's disease
资金
- Italian Ministry of Education, University, and Research (MIUR) - National Research Programme (PNR) - CNR Flagship InterOmics'' Project [PB.P05]
- PNR - CNR Aging program
- Lombardy Region - CNR
- MbMM Project [18089/RCC]
- MIUR-Research Projects of National Interest (PRIN) [2010M2JARJ]
- FONDECYT [1100165]
- Parkinson's Disease Foundation
- JPB Foundation
- NIH [DA07418, DA10154]
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. (C) 2015 Elsevier Ltd. All rights reserved.
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