A proposed dual role of neuromelanin in the pathogenesis of Parkinson's disease.
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.
Zecca
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L
Institute of Biomedical Technologies-Italian Research Council, Segrate, Milano, Italy. luigi.zecca@itb.cnr.it
Zucca
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FA
Albertini
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A
Rizzio
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Fariello
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RG
D000375:Aging; D000818:Animals; D018450:Disease Progression; D006801:Humans; D008543:Melanins / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D010300:Parkinson Disease / Q000209:etiology*
D008543:Melanins; C014121:neuromelanin