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Melanin affinity and its possible role in neurodegeneration
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Drug Safety and Toxicology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Drug Safety and Toxicology)
2013 (English)In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 120, no 12, 1623-1630 p.Article, review/survey (Refereed) Published
Abstract [en]

Certain drugs with melanin affinity are known to have caused pigmentary lesions in the eye and skin. This was the basis for the hypothesis that compounds with melanin affinity may cause damage also in other melanin-bearing tissues such as the substantia nigra. The heterogeneity of compounds that binds to melanin is large. Toxins, drugs, and several other compounds have melanin affinity. Compounds showing the highest affinity are mainly organic amines and metal ions. The binding of toxicants to melanin probably protects the cells initially. However, the binding is normally, slowly reversible and melanin may accumulate the toxicant and gradually release it into the cytosol. Several studies indicate that neuromelanin may play a significant role both in the initiation and in the progression of neurodegeneration. MPTP/MPP(+) that has been causally linked with Parkinsonism has high affinity for neuromelanin, and the induced dopaminergic denervation correlates with the neuromelanin content in the cells. This shows that the toxicological implications of the accumulation of toxicants in pigmented neurons and its possible role in neurodegeneration should not be neglected. Extracellular neuromelanin has been reported to activate dendritic cells and microglia. An initial neuronal damage induced by a neurotoxicant that leaks neuromelanin from the cells may therefore lead to a vicious cycle of neuroinflammation and further neurodegeneration. Although there are many clues to the particular vulnerability of dopaminergic neurons of substantia nigra in Parkinson's disease, the critical factors are not known. Further studies to determine the importance of neuromelanin in neurodegeneration and Parkinson's disease are warranted.

Place, publisher, year, edition, pages
2013. Vol. 120, no 12, 1623-1630 p.
National Category
Medical and Health Sciences Natural Sciences
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URN: urn:nbn:se:uu:diva-210041DOI: 10.1007/s00702-013-1062-5ISI: 000327392700001PubMedID: 23821370OAI: oai:DiVA.org:uu-210041DiVA: diva2:660604
Available from: 2013-10-30 Created: 2013-10-30 Last updated: 2017-12-06Bibliographically approved

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Karlsson, Oskar

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