Neurology. 2006 Oct 10;67(7 Suppl 2):S8-11. Related Articles, Links


A proposed dual role of neuromelanin in the pathogenesis of Parkinson's disease.

Zecca L, Zucca FA, Albertini A, Rizzio E, Fariello RG.

Institute of Biomedical Technologies-Italian Research Council, Segrate, Milano, Italy. luigi.zecca@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-alpha, 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.

PMID: 17030740 [PubMed - in process]