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© 2006 American Academy of Neurology
A proposed dual role of neuromelanin in the pathogenesis of Parkinson’s diseaseFrom the Institute of Biomedical Technologies-Italian Research Council, Segrate, Italy (L.Z., F.A.Z., A.A.), National Institute of Metrology, Unit of Radiochemistry and Spectroscopy, Pavia, Italy (E.R.), and Newron Pharmaceuticals R&D Department, Bresso (Milano), Italy (R.G.F.). Address correspondence and reprint requests to Dr. Luigi Zecca, Institute of Biomedical Technologies-CNR, Via Cervi, 93, 20090 Segrate (Milano), Italy; e-mail: luigi.zecca{at}itb.cnr.it
In many parkinsonian syndromes, neuromelanin (NM)-containing dopaminergic neurons of the substantia nigra (SN) are selectively targeted by the noxius pathogens. Studies of the constitutional and functional features of human NM allow the formulation of a logical hypothesis on its role in parkinsonian syndromes. In the early stages, NM synthesis and iron-chelating properties may act as a powerful protective mechanism, delaying symptom appearance and/or slowing disease progression. Once these systems have been exhausted, the pathogenic mechanisms affecting cytoplasmic organelles other than NM destroy NM-harboring neurons, with consequent pouring out of NM granules. These in turn activate microglia, causing release of nitric oxide, interleukin-6 and tumor necrosis factor-
This study was supported by grants of MIUR-FIRB project RBNE03PX83_002 on Protein Folding and Aggregation: Metal and Biomolecules in Protein Conformational Diseases and MIUR-PRIN project 2005035582 on Chemical Processes and Structural Modifications in Neurodegeneration. Publication of this supplement was supported by a grant from Newron Pharmaceuticals. Disclosure: R.G.F. was an employee of the sponsor until May 2005. A.A., E.R., F.A.Z., and L.Z., report no conflicts of interest.
Neurology supplements are not peer-reviewed. Information contained in Neurology supplements represents the opinions of the authors and is not endorsed by nor does it reflect the views of the American Academy of Neurology, Editorial Board, Editor-in-Chief, or Associate Editors of Neurology. This article has been cited by other articles:
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, thus becoming an important determinant of disease aggravation. Neuromelanin appears to be a suitable target for devising chemical agents that might modify the course of these diseases. 
