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pubmed-article:17030740pubmed:abstractTextIn 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.lld:pubmed
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pubmed-article:17030740pubmed:articleTitleA proposed dual role of neuromelanin in the pathogenesis of Parkinson's disease.lld:pubmed
pubmed-article:17030740pubmed:affiliationInstitute of Biomedical Technologies-Italian Research Council, Segrate, Milano, Italy. luigi.zecca@itb.cnr.itlld:pubmed
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