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