Neurotoxicity Research

, Volume 25, Issue 1, pp 13–23 | Cite as

Neuromelanin of the Human Substantia Nigra: An Update

  • Fabio A. Zucca
  • Emy Basso
  • Francesca A. Cupaioli
  • Emanuele Ferrari
  • David Sulzer
  • Luigi Casella
  • Luigi ZeccaEmail author
Review Article


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.


Neuromelanin 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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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Fabio A. Zucca
    • 1
  • Emy Basso
    • 1
  • Francesca A. Cupaioli
    • 1
  • Emanuele Ferrari
    • 1
  • David Sulzer
    • 3
  • Luigi Casella
    • 2
  • Luigi Zecca
    • 1
    Email author
  1. 1.Institute of Biomedical TechnologiesNational Research Council of ItalySegrate (MI)Italy
  2. 2.Department of ChemistryUniversity of PaviaPaviaItaly
  3. 3.Department of Psychiatry, Neurology and PharmacologyColumbia UniversityNew YorkUSA

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