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Melanin and neuromelanin binding of drugs and chemicals: toxicological implications
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Karolinska Inst, Dept Clin Neurosci, Ctr Mol Med, S-17176 Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2016 (English)In: Archives of Toxicology, ISSN 0340-5761, E-ISSN 1432-0738, Vol. 90, no 8, 1883-1891 p.Article, review/survey (Refereed) PublishedText
Abstract [en]

Melanin is a polyanionic pigment that colors, e.g., the hair, skin and eyes. The pigment neuromelanin is closely related to melanin and is mainly produced in specific neurons of the substantia nigra. Certain drugs and chemicals bind to melanin/neuromelanin and are retained in pigment cells for long periods. This specific retention is thought to protect the cells but also to serve as a depot that slowly releases accumulated compounds and may cause toxicity in the eye and skin. Moreover, neuromelanin and compounds with high neuromelanin affinity have been suggested to be implicated in the development of adverse drug reactions in the central nervous system (CNS) as well as in the etiology of Parkinson's disease (PD). Epidemiologic studies implicate the exposure to pesticides, metals, solvents and other chemicals as risk factors for PD. Neuromelanin interacts with several of these toxicants which may play a significant part in both the initiation and the progression of neurodegeneration. MPTP/MPP+ that has been casually linked with parkinsonism has high affinity for neuromelanin, and the induced dopaminergic denervation correlates with the neuromelanin content in the cells. Recent studies have also reported that neuromelanin may interact with alpha-synuclein as well as activate microglia and dendritic cells. This review aims to provide an overview of melanin binding of drugs and other compounds, and possible toxicological implications, with particular focus on the CNS and its potential involvement in neurodegenerative disorders.

Place, publisher, year, edition, pages
2016. Vol. 90, no 8, 1883-1891 p.
Keyword [en]
ALS/PDC, BMAA, Pesticides, MPTP, Neuromelanin, Parkinson's disease, Retinopathy
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-300651DOI: 10.1007/s00204-016-1757-0ISI: 000379254500007PubMedID: 27311820OAI: oai:DiVA.org:uu-300651DiVA: diva2:951860
Available from: 2016-08-10 Created: 2016-08-10 Last updated: 2016-08-10Bibliographically approved

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