Neuromelanin of the Human Substantia Nigra: An Update
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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.
KeywordsNeuromelanin Substantia nigra Parkinson’s disease Aging Neuroinflammation Neurodegeneration
EB, FAC, EF, LZ, and FAZ were supported by Italian Ministry of Education, University, and Research (MIUR)–National Research Programme (PNR)–CNR Flagship “InterOmics” Project (PB.P05), by PNR–CNR Aging program 2012–2014 and by MIUR–Medical Research in Italy (MERIT) Project RBNE08ZZN7. DS’s effort is supported by the Udall Center of Excellence in Parkinson’s disease, and the Parkinson’s disease and JPB Foundations. LC and LZ also acknowledge the MIUR–Research Projects of National Interest (PRIN) 2012–2011 prot. 2010M2JARJ.
Conflict of interest
All authors declare no conflicts of interest.
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