Potential Roles of Accelerated Dopamine Oxidation, Altered Glutathione Metabolism, 5-S-Cysteinyl-Dopamine and its Oxidative Metabolites in the Pathogenesis of Parkinson’s Disease

Dryhurst, Glenn; Shen, Xue-Ming; Li, Hong; Yang, Zhifei; Han, Jilin; Cheng, Fu‐Chou

doi:10.1007/978-1-4615-1269-1_19

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“…As yet, however, too little information is available to assess whether NM in the parkinsonian brain differs from that in the healthy brain. In this context it is interesting to note that Dryhurst et al (2000) hypothesized that NM is not polymerized in the parkinsonian brain, because the dopamine-o-quinone, a product of intraneuronal dopamine oxidation, is scavenged by translocated cysteine. It is also of interest that Kastner et al (1992) report that in PD, pigmented cells contain less NM that that found in healthy brains, a suggestion also made by Aime et al (2000).…”

Section: Neuromelanin and Degeneration Of Dopaminergic Neuronsmentioning

confidence: 99%

Neuromelanin and its interaction with iron as a potential risk factor for dopaminergic neurodegeneration underlying Parkinson's disease

et al. 2003

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Neuromelanin (NM) is a granular, dark brown pigment produced in some but not all of the dopaminergic neurons of the human substantia nigra (SN). In Parkinson's disease (PD) the pigmented dopaminergic neurons of the SN degenerate, suggesting that this process is related to the presence of NM. As yet it is unknown whether NM in the parkinsonian brain differs from that found in healthy tissue and thus may fulfil a different role within this tissue. The function of NM within the pigmented neurons is unknown but other melanins are believed to play a protective role via attenuation of free radical damage. Experimental evidence suggests that NM may also exhibit this characteristic, possibly by direct inactivation of free radical species or via its ability to chelate transition metals, such as iron. NM has the ability to bind a variety of metals, seven per cent of isolated NM is reported to consist of Fe, Cu, Zn and Cr. Iron is of particular interest as this metal is highly concentrated within the SN. Up to 20 per cent of the total iron contained in the SN from normal subjects is bound within NM. Further, it was demonstrated that NM contains a protein component and that iron is bound to NM in the ferric form. Increased tissue iron found in the parkinsonian SN may saturate iron-chelating sites on NM, and a looser association between iron and NM may result in an increased, rather than decreased, production of free radical species. It is hypothesized that this redox-active iron could be released and involved in a Fenton-like reaction leading to an increased production of oxidative radicals. The resultant radical-mediated cytotoxicity may contribute to cellular damage observed in PD.

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Section: Neuromelanin and Degeneration Of Dopaminergic Neuronsmentioning

confidence: 99%