{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:05:25Z","timestamp":1791165925225,"version":"4.1.0"},"reference-count":129,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2016,6,16]],"date-time":"2016-06-16T00:00:00Z","timestamp":1466035200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Toxicol"],"published-print":{"date-parts":[[2016,8]]},"DOI":"10.1007\/s00204-016-1757-0","type":"journal-article","created":{"date-parts":[[2016,6,16]],"date-time":"2016-06-16T13:40:57Z","timestamp":1466084457000},"page":"1883-1891","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Melanin and neuromelanin binding of drugs and chemicals: toxicological implications"],"prefix":"10.1007","volume":"90","author":[{"given":"Oskar","family":"Karlsson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils Gunnar","family":"Lindquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,16]]},"reference":[{"key":"1757_CR1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0378-4347(01)00486-8","volume":"768","author":"AF Aubry","year":"2002","unstructured":"Aubry AF (2002) Applications of affinity chromatography to the study of drug-melanin binding interactions. J Chromatogr B Analyt Technol Biomed Life Sci 768:67\u201374","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"1757_CR2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.toxlet.2014.01.039","volume":"230","author":"MT Baltazar","year":"2014","unstructured":"Baltazar MT, Dinis-Oliveira RJ, de Lourdes Bastos M, Tsatsakis AM, Duarte JA, Carvalho F (2014) Pesticides exposure as etiological factors of Parkinson\u2019s disease and other neurodegenerative diseases\u2013a mechanistic approach. Toxicol Lett 230:85\u2013103","journal-title":"Toxicol Lett"},{"key":"1757_CR3","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1212\/01.WNL.0000078320.18564.9F","volume":"61","author":"SA Banack","year":"2003","unstructured":"Banack SA, Cox PA (2003) Biomagnification of cycad neurotoxins in flying foxes: implications for ALS-PDC in Guam. Neurology 61:387\u2013389","journal-title":"Neurology"},{"key":"1757_CR4","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/0361-9230(83)90218-6","volume":"10","author":"H Barden","year":"1983","unstructured":"Barden H, Levine S (1983) Histochemical observations on rodent brain melanin. Brain Res Bull 10:847\u2013851","journal-title":"Brain Res Bull"},{"key":"1757_CR5","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1001\/archneurol.2010.1","volume":"67","author":"JM Bertoni","year":"2010","unstructured":"Bertoni JM, Arlette JP, Fernandez HH et al (2010) Increased melanoma risk in Parkinson disease: a prospective clinicopathological study. Arch Neurol 67:347\u2013352","journal-title":"Arch Neurol"},{"key":"1757_CR6","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1212\/01.wnl.0000344257.59693.cf","volume":"72","author":"AR Borenstein","year":"2009","unstructured":"Borenstein AR, Mortimer JA, Schellenberg GD, Galasko D (2009) The ALS\/PDC syndrome of Guam and the cycad hypothesis. Neurology 72:473","journal-title":"Neurology"},{"key":"1757_CR7","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S1011-1344(01)00227-5","volume":"64","author":"M Boulton","year":"2001","unstructured":"Boulton M, Rozanowska M, Rozanowski B (2001) Retinal photodamage. J Photochem Photobiol, B 64:144\u2013161","journal-title":"J Photochem Photobiol, B"},{"key":"1757_CR8","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1212\/01.wnl.0000344257.59693.cf","volume":"72","author":"WG Bradley","year":"2009","unstructured":"Bradley WG, Banack SA, Cox PA (2009) The ALS\/PDC syndrome of Guam and the cycad hypothesis. Neurology 72:473\u2013474","journal-title":"Neurology"},{"key":"1757_CR9","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0161-6420(93)31696-9","volume":"100","author":"RJ Campbell","year":"1993","unstructured":"Campbell RJ, Steele JC, Cox TA, Loerzel AJ, Belli M, Belli DD, Kurland LT (1993) Pathologic findings in the retinal pigment epitheliopathy associated with the amyotrophic lateral sclerosis\/parkinsonism-dementia complex of Guam. Ophthalmology 100:37\u201342","journal-title":"Ophthalmology"},{"key":"1757_CR10","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1038\/ncomms4633","volume":"5","author":"C Cebrian","year":"2014","unstructured":"Cebrian C, Zucca FA, Mauri P et al (2014) MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration. Nat commun 5:3633","journal-title":"Nat commun"},{"key":"1757_CR11","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s10540-006-9028-6","volume":"26","author":"F Copped\u00e8","year":"2006","unstructured":"Copped\u00e8 F, Mancuso M, Siciliano G, Migliore L, Murri L (2006) Genes and the environment in neurodegeneration. Biosci Rep 26:341\u2013367","journal-title":"Biosci Rep"},{"key":"1757_CR12","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1016\/S0161-6420(89)32656-X","volume":"96","author":"TA Cox","year":"1989","unstructured":"Cox TA, McDarby JV, Lavine L, Steele JC, Calne DB (1989) A retinopathy on Guam with high prevalence in Lytico-Bodig. Ophthalmology 96:1731\u20131735","journal-title":"Ophthalmology"},{"key":"1757_CR13","doi-asserted-by":"crossref","unstructured":"Cox, PA., Davis, DA, Mash, DC, Metcalf, JS Banack, SA (2016) Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain. In: Proceedings of the biological sciences\/The Royal Society,vol 283","DOI":"10.1098\/rspb.2015.2397"},{"key":"1757_CR14","first-page":"474","volume":"72","author":"R Cruz-Aguado","year":"2009","unstructured":"Cruz-Aguado R, Shaw CA (2009) The ALS\/PDC syndrome of Guam and the cycad hypothesis. Neurology 72:474","journal-title":"Neurology"},{"key":"1757_CR15","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1126\/science.3080808","volume":"231","author":"RJ D\u2019Amato","year":"1986","unstructured":"D\u2019Amato RJ, Lipman ZP, Snyder SH (1986) Selectivity of the parkinsonian neurotoxin MPTP: toxic metabolite MPP\u00a0+\u00a0binds to neuromelanin. Science 231:987\u2013989","journal-title":"Science"},{"key":"1757_CR16","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/327324a0","volume":"327","author":"RJ D\u2019Amato","year":"1987","unstructured":"D\u2019Amato RJ, Alexander GM, Schwartzman RJ, Kitt CA, Price DL, Snyder SH (1987) Evidence for neuromelanin involvement in MPTP-induced neurotoxicity. Nature 327:324\u2013326","journal-title":"Nature"},{"key":"1757_CR17","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1080\/10915810290169873","volume":"21","author":"P Dayhaw-Barker","year":"2002","unstructured":"Dayhaw-Barker P (2002) Retinal pigment epithelium melanin and ocular toxicity. Int J Toxicol 21:451\u2013454","journal-title":"Int J Toxicol"},{"key":"1757_CR18","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S1474-4422(06)70471-9","volume":"5","author":"LM Lau de","year":"2006","unstructured":"de Lau LM, Breteler MM (2006) Epidemiology of Parkinson\u2019s disease. Lancet Neurol 5:525\u2013535","journal-title":"Lancet Neurol"},{"key":"1757_CR19","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1080\/10408440701669959","volume":"38","author":"RJ Dinis-Oliveira","year":"2008","unstructured":"Dinis-Oliveira RJ, Duarte JA, S\u00e1nchez-Navarro A, Remi\u00e3o F, Bastos ML, Carvalho F (2008) Paraquat poisonings: mechanisms of lung toxicity, clinical features, and treatment. Crit Rev Toxicol 38:13\u201371","journal-title":"Crit Rev Toxicol"},{"key":"1757_CR20","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/S0892-0362(02)00218-0","volume":"24","author":"KL Double","year":"2002","unstructured":"Double KL, Ben-Shachar D, Youdim MB, Zecca L, Riederer P, Gerlach M (2002) Influence of neuromelanin on oxidative pathways within the human substantia nigra. Neurotoxicol Teratol 24:621\u2013628","journal-title":"Neurotoxicol Teratol"},{"key":"1757_CR21","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S0006-2952(03)00293-4","volume":"66","author":"KL Double","year":"2003","unstructured":"Double KL, Gerlach M, Schunemann V, Trautwein AX, Zecca L, Gallorini M, Youdim MB, Riederer P, Ben-Shachar D (2003) Iron-binding characteristics of neuromelanin of the human substantia nigra. Biochem Pharmacol 66:489\u2013494","journal-title":"Biochem Pharmacol"},{"key":"1757_CR22","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.expneurol.2009.03.002","volume":"217","author":"KL Double","year":"2009","unstructured":"Double KL, Rowe DB, Carew-Jones FM et al (2009) Anti-melanin antibodies are increased in sera in Parkinson\u2019s disease. Exp Neurol 217:297\u2013301","journal-title":"Exp Neurol"},{"key":"1757_CR23","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1097\/00005072-196507000-00003","volume":"24","author":"P Duffy","year":"1965","unstructured":"Duffy P, Tennyson VM (1965) Phase and electron microscopic observations of Lewy bodies and melanin granules in the substantia nigra and locus Caeruleus in Parkinson\u2019s Disease. J Neuropathol Exp Neurol 24:398\u2013414","journal-title":"J Neuropathol Exp Neurol"},{"key":"1757_CR24","doi-asserted-by":"crossref","first-page":"e48490","DOI":"10.1371\/journal.pone.0048490","volume":"7","author":"M Engelen","year":"2012","unstructured":"Engelen M, Vanna R, Bellei C, Zucca FA, Wakamatsu K, Monzani E, Ito S, Casella L, Zecca L (2012) Neuromelanins of human brain have soluble and insoluble components with dolichols attached to the melanic structure. PLoS ONE 7:e48490","journal-title":"PLoS ONE"},{"key":"1757_CR25","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1046\/j.1471-4159.2003.01923.x","volume":"86","author":"BA Faucheux","year":"2003","unstructured":"Faucheux BA, Martin ME, Beaumont C, Hauw JJ, Agid Y, Hirsch EC (2003) Neuromelanin associated redox-active iron is increased in the substantia nigra of patients with Parkinson\u2019s disease. J Neurochem 86:1142\u20131148","journal-title":"J Neurochem"},{"key":"1757_CR26","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.neurobiolaging.2005.02.015","volume":"27","author":"H Fedorow","year":"2006","unstructured":"Fedorow H, Halliday GM, Rickert CH, Gerlach M, Riederer P, Double KL (2006) Evidence for specific phases in the development of human neuromelanin. Neurobiol Aging 27:506\u2013512","journal-title":"Neurobiol Aging"},{"key":"1757_CR27","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1212\/WNL.18.8.817","volume":"18","author":"GM Fenichel","year":"1968","unstructured":"Fenichel GM, Bazelon M (1968) Studies on neuromelanin. II. Melanin in the brainstems of infants and children. Neurology 18:817\u2013820","journal-title":"Neurology"},{"key":"1757_CR28","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.cbi.2010.06.003","volume":"188","author":"R Franco","year":"2010","unstructured":"Franco R, Li S, Rodriguez-Rocha H, Burns M, Panayiotidis MI (2010) Molecular mechanisms of pesticide-induced neurotoxicity: relevance to Parkinson\u2019s disease. Chem Biol Interact 188:289\u2013300","journal-title":"Chem Biol Interact"},{"key":"1757_CR29","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.envint.2014.11.002","volume":"75","author":"M Furlong","year":"2015","unstructured":"Furlong M, Tanner CM, Goldman SM et al (2015) Protective glove use and hygiene habits modify the associations of specific pesticides with Parkinson\u2019s disease. Environ Int 75:144\u2013150","journal-title":"Environ Int"},{"key":"1757_CR30","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1212\/WNL.0b013e3181bd13a1","volume":"73","author":"X Gao","year":"2009","unstructured":"Gao X, Simon KC, Han J, Schwarzschild MA, Ascherio A (2009) Family history of melanoma and Parkinson disease risk. Neurology 73:1286\u20131291","journal-title":"Neurology"},{"key":"1757_CR31","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/0022-510X(83)90221-6","volume":"58","author":"P Gaspar","year":"1983","unstructured":"Gaspar P, Berger B, Gay M, Hamon M, Cesselin F, Vigny A, Javoy-Agid F, Agid Y (1983) Tyrosine hydroxylase and methionine-enkephalin in the human mesencephalon. Immunocytochemical localization and relationships. J Neurol Sci 58:247\u2013267","journal-title":"J Neurol Sci"},{"key":"1757_CR32","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/j.1471-4159.2005.03019.x","volume":"93","author":"E Greggio","year":"2005","unstructured":"Greggio E, Bergantino E, Carter D et al (2005) Tyrosinase exacerbates dopamine toxicity but is not genetically associated with Parkinson\u2019s disease. J Neurochem 93:246\u2013256","journal-title":"J Neurochem"},{"key":"1757_CR33","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1093\/brain\/awh584","volume":"128","author":"GM Halliday","year":"2005","unstructured":"Halliday GM, Ophof A, Broe M et al (2005) Alpha-synuclein redistributes to neuromelanin lipid in the substantia nigra early in Parkinson\u2019s disease. Brain 128:2654\u20132664","journal-title":"Brain"},{"key":"1757_CR34","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s00702-006-0449-y","volume":"113","author":"GM Halliday","year":"2006","unstructured":"Halliday GM, Fedorow H, Rickert CH, Gerlach M, Riederer P, Double KL (2006) Evidence for specific phases in the development of human neuromelanin. J Neural Transm 113:721\u2013728","journal-title":"J Neural Transm"},{"key":"1757_CR35","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.mehy.2008.10.011","volume":"72","author":"EH Hernandez","year":"2009","unstructured":"Hernandez EH (2009) Pigmentation genes link Parkinson\u2019s disease to melanoma, opening a window on both etiologies. Med Hypotheses 72:280\u2013284","journal-title":"Med Hypotheses"},{"key":"1757_CR36","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/0306-4522(93)90349-K","volume":"56","author":"MT Herrero","year":"1993","unstructured":"Herrero MT, Hirsch EC, Kastner A, Ruberg M, Luquin MR, Laguna J, Javoy-Agid F, Obeso JA, Agid Y (1993) Does neuromelanin contribute to the vulnerability of catecholaminergic neurons in monkeys intoxicated with MPTP? Neuroscience 56:499\u2013511","journal-title":"Neuroscience"},{"key":"1757_CR37","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/334345a0","volume":"334","author":"E Hirsch","year":"1988","unstructured":"Hirsch E, Graybiel AM, Agid YA (1988) Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson\u2019s disease. Nature 334:345\u2013348","journal-title":"Nature"},{"key":"1757_CR38","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/j.1751-1097.2008.00316.x","volume":"84","author":"DN Hu","year":"2008","unstructured":"Hu DN, Simon JD, Sarna T (2008) Role of ocular melanin in ophthalmic physiology and pathology. Photochem Photobiol 84:639\u2013644","journal-title":"Photochem Photobiol"},{"key":"1757_CR39","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1111\/j.1471-4159.2009.06011.x","volume":"109","author":"LZ Huang","year":"2009","unstructured":"Huang LZ, Parameswaran N, Bordia T, Michael McIntosh J, Quik M (2009) Nicotine is neuroprotective when administered before but not after nigrostriatal damage in rats and monkeys. J Neurochem 109:826\u2013837","journal-title":"J Neurochem"},{"issue":"Suppl 3","key":"1757_CR40","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/PL00007745","volume":"245","author":"A Ishikawa","year":"1998","unstructured":"Ishikawa A, Takahashi H (1998) Clinical and neuropathological aspects of autosomal recessive juvenile parkinsonism. J Neurol 245(Suppl 3):4\u20139","journal-title":"J Neurol"},{"key":"1757_CR41","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1034\/j.1600-0749.2003.00037.x","volume":"16","author":"S Ito","year":"2003","unstructured":"Ito S (2003) A chemist\u2019s view of melanogenesis. Pigment Cell Res 16:230\u2013236","journal-title":"Pigment Cell Res"},{"key":"1757_CR42","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1111\/j.1751-1097.2007.00238.x","volume":"84","author":"S Ito","year":"2008","unstructured":"Ito S, Wakamatsu K (2008) Chemistry of mixed melanogenesis\u2013pivotal roles of dopaquinone. Photochem Photobiol 84:582\u2013592","journal-title":"Photochem Photobiol"},{"key":"1757_CR43","first-page":"267","volume":"60","author":"KA Jellinger","year":"1993","unstructured":"Jellinger KA, Kienzl E, Rumpelmaier G, Paulus W, Riederer P, Stachelberger H, Youdim MB, Ben-Shachar D (1993) Iron and ferritin in substantia nigra in Parkinson\u2019s disease. Adv Neurol 60:267\u2013272","journal-title":"Adv Neurol"},{"key":"1757_CR44","doi-asserted-by":"crossref","first-page":"9","DOI":"10.2302\/kjm.44.9","volume":"44","author":"K Jimbow","year":"1995","unstructured":"Jimbow K (1995) Current update and trends in melanin pigmentation and melanin biology. Keio J Med 44:9\u201318","journal-title":"Keio J Med"},{"key":"1757_CR45","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1007\/s00702-013-1062-5","volume":"120","author":"O Karlsson","year":"2013","unstructured":"Karlsson O, Lindquist NG (2013) Melanin affinity and its possible role in neurodegeneration. J Neural Transm 120:1623\u20131630","journal-title":"J Neural Transm"},{"key":"1757_CR46","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/j.1755-148X.2008.00508.x","volume":"22","author":"O Karlsson","year":"2009","unstructured":"Karlsson O, Berg C, Brittebo EB, Lindquist NG (2009) Retention of the cyanobacterial neurotoxin beta-N-methylamino-l-alanine in melanin and neuromelanin-containing cells\u2013a possible link between Parkinson-dementia complex and pigmentary retinopathy. Pigment Cell Melanoma Res 22:120\u2013130","journal-title":"Pigment Cell Melanoma Res"},{"key":"1757_CR47","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s00204-014-1262-2","volume":"89","author":"O Karlsson","year":"2015","unstructured":"Karlsson O, Berg AL, Hanrieder J, Arnerup G, Lindstrom AK, Brittebo EB (2015) Intracellular fibril formation, calcification, and enrichment of chaperones, cytoskeletal, and intermediate filament proteins in the adult hippocampus CA1 following neonatal exposure to the nonprotein amino acid BMAA. Arch Toxicol 89:423\u2013436","journal-title":"Arch Toxicol"},{"key":"1757_CR48","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1111\/j.1471-4159.1992.tb08350.x","volume":"59","author":"A Kastner","year":"1992","unstructured":"Kastner A, Hirsch EC, Lejeune O, Javoy-Agid F, Rascol O, Agid Y (1992) Is the vulnerability of neurons in the substantia nigra of patients with Parkinson\u2019s disease related to their neuromelanin content? J Neurochem 59:1080\u20131089","journal-title":"J Neurochem"},{"key":"1757_CR49","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s10633-007-9105-6","volume":"116","author":"U Kellner","year":"2008","unstructured":"Kellner U, Kellner S, Weinitz S (2008) Chloroquine retinopathy: lipofuscin- and melanin-related fundus autofluorescence, optical coherence tomography and multifocal electroretinography. Doc Ophthalmol 116:119\u2013127","journal-title":"Doc Ophthalmol"},{"key":"1757_CR50","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.forsciint.2011.10.018","volume":"218","author":"P Kintz","year":"2012","unstructured":"Kintz P (2012) Value of the concept of minimal detectable dosage in human hair. Forensic Sci Int 218:28\u201330","journal-title":"Forensic Sci Int"},{"key":"1757_CR51","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1254\/jjp.84.237","volume":"84","author":"Y Kitamura","year":"2000","unstructured":"Kitamura Y, Shimohama S, Akaike A, Taniguchi T (2000) The parkinsonian models: invertebrates to mammals. Jpn J Pharmacol 84:237\u2013243","journal-title":"Jpn J Pharmacol"},{"key":"1757_CR52","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1146\/annurev.ne.11.030188.000501","volume":"11","author":"IJ Kopin","year":"1988","unstructured":"Kopin IJ, Markey SP (1988) MPTP toxicity: implications for research in Parkinson\u2019s disease. Annu Rev Neurosci 11:81\u201396","journal-title":"Annu Rev Neurosci"},{"key":"1757_CR53","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s00702-012-0842-7","volume":"120","author":"E Koutsilieri","year":"2013","unstructured":"Koutsilieri E, Lutz MB, Scheller C (2013) Autoimmunity, dendritic cells and relevance for Parkinson\u2019s disease. J Neural Transm 120:75\u201381","journal-title":"J Neural Transm"},{"key":"1757_CR54","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1126\/science.6823561","volume":"219","author":"JW Langston","year":"1983","unstructured":"Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219:979\u2013980","journal-title":"Science"},{"key":"1757_CR55","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/1531-8249(199910)46:4<598::AID-ANA7>3.0.CO;2-F","volume":"46","author":"JW Langston","year":"1999","unstructured":"Langston JW, Forno LS, Tetrud J, Reeves AG, Kaplan JA, Karluk D (1999) Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann Neurol 46:598\u2013605","journal-title":"Ann Neurol"},{"key":"1757_CR56","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/j.1600-0749.1993.tb00591.x","volume":"6","author":"BS Larsson","year":"1993","unstructured":"Larsson BS (1993) Interaction between chemicals and melanin. Pigment Cell Res 6:127\u2013133","journal-title":"Pigment Cell Res"},{"key":"1757_CR57","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/0006-2952(79)90326-5","volume":"28","author":"B Larsson","year":"1979","unstructured":"Larsson B, Tjalve H (1979) Studies on the mechanism of drug-binding to melanin. Biochem Pharmacol 28:1181\u20131187","journal-title":"Biochem Pharmacol"},{"key":"1757_CR58","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1006\/rtph.1998.1243","volume":"28","author":"B Leblanc","year":"1998","unstructured":"Leblanc B, Jezequel S, Davies T, Hanton G, Taradach C (1998) Binding of drugs to eye melanin is not predictive of ocular toxicity. Regul Toxicol Pharmacol RTP 28:124\u2013132","journal-title":"Regul Toxicol Pharmacol RTP"},{"key":"1757_CR59","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s00702-011-0753-z","volume":"119","author":"J Li","year":"2012","unstructured":"Li J, Yang J, Zhao P, Li S, Zhang R, Zhang X, Liu D, Zhang B (2012) Neuromelanin enhances the toxicity of alpha-synuclein in SK-N-SH cells. J Neural Transm 119:685\u2013691","journal-title":"J Neural Transm"},{"key":"1757_CR60","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/cne.20098","volume":"473","author":"CL Liang","year":"2004","unstructured":"Liang CL, Nelson O, Yazdani U, Pasbakhsh P, German DC (2004) Inverse relationship between the contents of neuromelanin pigment and the vesicular monoamine transporter-2: human midbrain dopamine neurons. J Comp Neurol 473:97\u2013106","journal-title":"J Comp Neurol"},{"key":"1757_CR61","first-page":"190","volume":"200","author":"NG Lindquist","year":"1972","unstructured":"Lindquist NG (1972) Accumulation in vitro of 35 S-chlorpromazine in the neuromelanin of human substantia nigra and locus coeruleus. Arch internationales de pharmacodynamie et de therapie 200:190\u2013195","journal-title":"Arch internationales de pharmacodynamie et de therapie"},{"key":"1757_CR62","first-page":"1","volume":"325","author":"NG Lindquist","year":"1973","unstructured":"Lindquist NG (1973) Accumulation of drugs on melanin. Acta Radiol Diagn (Stockh) 325:1\u201392","journal-title":"Acta Radiol Diagn (Stockh)"},{"key":"1757_CR63","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1600-0773.1986.tb00149.x","volume":"59","author":"NG Lindquist","year":"1986","unstructured":"Lindquist NG, Lyden-Sokolowski A, Larsson BS (1986) Accumulation of a parkinsonism-inducing neurotoxin in melanin-bearing neurons: autoradiographic studies on 3H-MPTP. Acta pharmacologica et toxicologica 59:161\u2013164","journal-title":"Acta pharmacologica et toxicologica"},{"key":"1757_CR64","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1600-0749.1987.tb00403.x","volume":"1","author":"NG Lindquist","year":"1987","unstructured":"Lindquist NG, Larsson BS, Lyden-Sokolowski A (1987) Neuromelanin and its possible protective and destructive properties. Pigment Cell Res 1:133\u2013136","journal-title":"Pigment Cell Res"},{"key":"1757_CR65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0304-3940(88)90002-X","volume":"93","author":"NG Lindquist","year":"1988","unstructured":"Lindquist NG, Larsson BS, Lyden-Sokolowski A (1988) Autoradiography of [14C]paraquat or [14C]diquat in frogs and mice: accumulation in neuromelanin. Neurosci Lett 93:1\u20136","journal-title":"Neurosci Lett"},{"key":"1757_CR66","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1212\/WNL.0b013e31821e554e","volume":"76","author":"R Liu","year":"2011","unstructured":"Liu R, Gao X, Lu Y, Chen H (2011) Meta-analysis of the relationship between Parkinson disease and melanoma. Neurology 76:2002\u20132009","journal-title":"Neurology"},{"key":"1757_CR67","doi-asserted-by":"crossref","first-page":"3384","DOI":"10.1021\/mp400225s","volume":"10","author":"H Liu","year":"2013","unstructured":"Liu H, Liu S, Miao Z, Jiang H, Deng Z, Hong X, Cheng Z (2013) A novel aliphatic 18F-labeled probe for PET imaging of melanoma. Mol Pharm 10:3384\u20133391","journal-title":"Mol Pharm"},{"key":"1757_CR68","first-page":"230","volume":"259","author":"A Lyden","year":"1982","unstructured":"Lyden A, Larsson B, Lindquist NG (1982) Studies on the melanin affinity of haloperidol. Arch Int Pharmacodyn Ther 259:230\u2013243","journal-title":"Arch Int Pharmacodyn Ther"},{"key":"1757_CR69","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/j.1600-0773.1983.tb03446.x","volume":"53","author":"A Lyden","year":"1983","unstructured":"Lyden A, Bondesson U, Larsson BS, Lindquist NG (1983) Melanin affinity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, an inducer of chronic parkinsonism in humans. Acta Pharmacol Toxicol (Copenh) 53:429\u2013432","journal-title":"Acta Pharmacol Toxicol (Copenh)"},{"key":"1757_CR70","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3233\/JAD-2003-5208","volume":"5","author":"QL Ma","year":"2003","unstructured":"Ma QL, Chan P, Yoshii M, Ueda K (2003) Alpha-synuclein aggregation and neurodegenerative diseases. J Alzheimers Dis 5:139\u2013148","journal-title":"J Alzheimers Dis"},{"key":"1757_CR71","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1021\/acs.molpharmaceut.5b00783","volume":"13","author":"JA Manzanares","year":"2016","unstructured":"Manzanares JA, Rimpela AK, Urtti A (2016) Interpretation of ocular melanin drug binding assays. alternatives to the model of multiple classes of independent sites. Mol Pharm 13:1251\u20131257","journal-title":"Mol Pharm"},{"key":"1757_CR72","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/j.1600-0749.1999.tb00760.x","volume":"12","author":"U Mars","year":"1999","unstructured":"Mars U, Larsson BS (1999) Pheomelanin as a binding site for drugs and chemicals. Pigment Cell Res 12:266\u2013274","journal-title":"Pigment Cell Res"},{"key":"1757_CR73","first-page":"256","volume":"95","author":"CD Marsden","year":"1961","unstructured":"Marsden CD (1961) Pigmentation in the nucleus substantiae nigrae of mammals. J Anat 95:256\u2013261","journal-title":"J Anat"},{"key":"1757_CR74","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.chroma.2010.11.015","volume":"1218","author":"MP Marszall","year":"2011","unstructured":"Marszall MP, Bucinski A, Gorynski K, Proszowska A, Kaliszan R (2011) Magnetic beads method for determination of binding of drugs to melanin. J Chromatogr A 1218:229\u2013236","journal-title":"J Chromatogr A"},{"key":"1757_CR75","doi-asserted-by":"crossref","first-page":"e10481","DOI":"10.1371\/journal.pone.0010481","volume":"5","author":"Y Matsuo","year":"2010","unstructured":"Matsuo Y, Kamitani T (2010) Parkinson\u2019s disease-related protein, alpha-synuclein, in malignant melanoma. PLoS ONE 5:e10481","journal-title":"PLoS ONE"},{"key":"1757_CR76","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/cne.20036","volume":"471","author":"AL McCormack","year":"2004","unstructured":"McCormack AL, Di Monte DA, Delfani K, Irwin I, DeLanney LE, Langston WJ, Janson AM (2004) Aging of the nigrostriatal system in the squirrel monkey. J Comp Neurol 471:387\u2013395","journal-title":"J Comp Neurol"},{"key":"1757_CR77","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1080\/01926230601178199","volume":"35","author":"L Mecklenburg","year":"2007","unstructured":"Mecklenburg L, Schraermeyer U (2007) An overview on the toxic morphological changes in the retinal pigment epithelium after systemic compound administration. Toxicol Pathol 35:252\u2013267","journal-title":"Toxicol Pathol"},{"key":"1757_CR78","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2174\/1573412911309020002","volume":"9","author":"M Michal Piotr","year":"2013","unstructured":"Michal Piotr M, Anna P, Adam B, Roman K (2013) Affinity chromatography method for determination of binding of drugs to melanin and evaluation of side effect potential of antipsychotic agents. Curr Pharm Anal 9:131\u2013138","journal-title":"Curr Pharm Anal"},{"key":"1757_CR79","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/1471-2202-12-116","volume":"12","author":"U Oberlander","year":"2011","unstructured":"Oberlander U, Pletinckx K, Dohler A et al (2011) Neuromelanin is an immune stimulator for dendritic cells in vitro. BMC Neurosci 12:116","journal-title":"BMC Neurosci"},{"key":"1757_CR80","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s00702-003-0080-0","volume":"111","author":"A Ostergren","year":"2004","unstructured":"Ostergren A, Annas A, Skog K, Lindquist NG, Brittebo EB (2004) Long-term retention of neurotoxic beta-carbolines in brain neuromelanin. J Neural Transm 111:141\u2013157","journal-title":"J Neural Transm"},{"key":"1757_CR81","doi-asserted-by":"crossref","first-page":"e45183","DOI":"10.1371\/journal.pone.0045183","volume":"7","author":"T Pan","year":"2012","unstructured":"Pan T, Zhu J, Hwu WJ, Jankovic J (2012) The role of alpha-synuclein in melanin synthesis in melanoma and dopaminergic neuronal cells. PLoS ONE 7:e45183","journal-title":"PLoS ONE"},{"key":"1757_CR82","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1126\/science.276.5321.2045","volume":"276","author":"MH Polymeropoulos","year":"1997","unstructured":"Polymeropoulos MH, Lavedan C, Leroy E et al (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson\u2019s disease. Science 276:2045\u20132047","journal-title":"Science"},{"key":"1757_CR83","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s004140050031","volume":"110","author":"L Potsch","year":"1997","unstructured":"Potsch L, Skopp G, Rippin G (1997) A comparison of 3H-cocaine binding on melanin granules and human hair in vitro. Int J Legal Med 110:55\u201362","journal-title":"Int J Legal Med"},{"key":"1757_CR84","first-page":"522","volume":"1","author":"AM Potts","year":"1962","unstructured":"Potts AM (1962a) The concentration of phenothiazines in the eye of experimental animals. Invest Ophthalmol 1:522\u2013530","journal-title":"Invest Ophthalmol"},{"key":"1757_CR85","first-page":"517","volume":"60","author":"AM Potts","year":"1962","unstructured":"Potts AM (1962b) Uveal pigment and phenothiazine compounds. Trans Am Ophthalmol Soc 60:517\u2013552","journal-title":"Trans Am Ophthalmol Soc"},{"key":"1757_CR86","first-page":"399","volume":"3","author":"AM Potts","year":"1964","unstructured":"Potts AM (1964a) Further studies concerning the accumulation of polycyclic compounds on uveal melanin. Invest Ophthalmol 3:399\u2013404","journal-title":"Invest Ophthalmol"},{"key":"1757_CR87","first-page":"405","volume":"3","author":"AM Potts","year":"1964","unstructured":"Potts AM (1964b) The reaction of uveal pigment in vitro with polycyclic compounds. Invest Ophthalmol 3:405\u2013416","journal-title":"Invest Ophthalmol"},{"key":"1757_CR88","volume-title":"Melanins and melanogenesis","author":"G Prota","year":"1992","unstructured":"Prota G (1992) Melanins and melanogenesis. Academic Press Inc, San Diego"},{"key":"1757_CR89","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1093\/oxfordjournals.aje.a114515","volume":"125","author":"D Reed","year":"1987","unstructured":"Reed D, Labarthe D, Chen KM, Stallones R (1987) A cohort study of amyotrophic lateral sclerosis and parkinsonism-dementia on Guam and Rota. Am J Epidemiol 125:92\u2013100","journal-title":"Am J Epidemiol"},{"key":"1757_CR90","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1002\/jps.24680","volume":"104","author":"J Reilly","year":"2015","unstructured":"Reilly J, Williams SL, Forster CJ, Kansara V, End P, Serrano-Wu MH (2015) High-throughput melanin-binding affinity and in silico methods to aid in the prediction of drug exposure in ocular tissue. J Pharm Sci 104:3997\u20134001","journal-title":"J Pharm Sci"},{"key":"1757_CR91","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/S0891-5849(98)00234-2","volume":"26","author":"M Rozanowska","year":"1999","unstructured":"Rozanowska M, Sarna T, Land EJ, Truscott TG (1999) Free radical scavenging properties of melanin interaction of eu- and pheo-melanin models with reducing and oxidising radicals. Free Radic Biol Med 26:518\u2013525","journal-title":"Free Radic Biol Med"},{"key":"1757_CR92","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1089\/jop.1994.10.217","volume":"10","author":"MM Salazar-Bookaman","year":"1994","unstructured":"Salazar-Bookaman MM, Wainer I, Patil PN (1994) Relevance of drug-melanin interactions to ocular pharmacology and toxicology. J Ocul Pharmacol 10:217\u2013239","journal-title":"J Ocul Pharmacol"},{"key":"1757_CR93","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0014-4835(84)90104-0","volume":"38","author":"L Salminen","year":"1984","unstructured":"Salminen L, Urtti A (1984) Disposition of ophthalmic timolol in treated and untreated rabbit eyes. A multiple and single dose study. Exp Eye Res 38:203\u2013206","journal-title":"Exp Eye Res"},{"key":"1757_CR94","volume-title":"Development of the nervous system","author":"DH Sanes","year":"2006","unstructured":"Sanes DH, Reh TA, Harris WA (2006) Development of the nervous system. Academic Press, Elsevier"},{"key":"1757_CR95","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/1011-1344(92)85027-R","volume":"12","author":"T Sarna","year":"1992","unstructured":"Sarna T (1992) Properties and function of the ocular melanin\u2013a photobiophysical view. J Photochem Photobiol, B 12:215\u2013258","journal-title":"J Photochem Photobiol, B"},{"key":"1757_CR96","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1007\/s007020100004","volume":"108","author":"N Schmidt","year":"2001","unstructured":"Schmidt N, Ferger B (2001) Neurochemical findings in the MPTP model of Parkinson\u2019s disease. J Neural Transm 108:1263\u20131282","journal-title":"J Neural Transm"},{"key":"1757_CR97","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.toxrep.2014.10.019","volume":"1","author":"RL Schroeder","year":"2014","unstructured":"Schroeder RL, Gerber JP (2014) Chloroquine and hydroxychloroquine binding to melanin: some possible consequences for pathologies. Toxicol Rep 1:963\u2013968","journal-title":"Toxicol Rep"},{"key":"1757_CR98","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1111\/jnc.12686","volume":"129","author":"J Segura-Aguilar","year":"2014","unstructured":"Segura-Aguilar J, Paris I, Munoz P, Ferrari E, Zecca L, Zucca FA (2014) Protective and toxic roles of dopamine in Parkinson\u2019s disease. J Neurochem 129:898\u2013915","journal-title":"J Neurochem"},{"key":"1757_CR99","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1007\/s00702-004-0211-2","volume":"111","author":"M Shamoto-Nagai","year":"2004","unstructured":"Shamoto-Nagai M, Maruyama W, Akao Y et al (2004) Neuromelanin inhibits enzymatic activity of 26S proteasome in human dopaminergic SH-SY5Y cells. J Neural Transm 111:1253\u20131265","journal-title":"J Neural Transm"},{"key":"1757_CR100","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/j.1755-148X.2009.00610.x","volume":"22","author":"JD Simon","year":"2009","unstructured":"Simon JD, Peles D, Wakamatsu K, Ito S (2009) Current challenges in understanding melanogenesis: bridging chemistry, biological control, morphology, and function. Pigment Cell Melanoma Res 22:563\u2013579","journal-title":"Pigment Cell Melanoma Res"},{"key":"1757_CR101","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1155\/2014\/498276","volume":"2014","author":"F Solano","year":"2014","unstructured":"Solano F (2014) Melanins: skin pigments and much more-types, structural models, biological functions, and formation routes. New J Sci 2014:28","journal-title":"New J Sci"},{"key":"1757_CR102","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1126\/science.3603037","volume":"237","author":"PS Spencer","year":"1987","unstructured":"Spencer PS, Nunn PB, Hugon J, Ludolph AC, Ross SM, Roy DN, Robertson RC (1987) Guam amyotrophic lateral sclerosis-parkinsonism-dementia linked to a plant excitant neurotoxin. Science 237:517\u2013522","journal-title":"Science"},{"key":"1757_CR103","first-page":"474","volume":"72","author":"PS Spencer","year":"2009","unstructured":"Spencer PS, Palmer V, Kisby G (2009) The ALS\/PDC syndrome of Guam and the cycad hypothesis. Neurology 72:474\u2013475","journal-title":"Neurology"},{"key":"1757_CR104","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1212\/01.wnl.0000312571.81091.26","volume":"70","author":"JC Steele","year":"2008","unstructured":"Steele JC, McGeer PL (2008) The ALS\/PDC syndrome of Guam and the cycad hypothesis. Neurology 70:1984\u20131990","journal-title":"Neurology"},{"key":"1757_CR105","doi-asserted-by":"crossref","first-page":"11869","DOI":"10.1073\/pnas.97.22.11869","volume":"97","author":"D Sulzer","year":"2000","unstructured":"Sulzer D, Bogulavsky J, Larsen KE et al (2000) Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles. Proc Natl Acad Sci USA 97:11869\u201311874","journal-title":"Proc Natl Acad Sci USA"},{"key":"1757_CR106","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3109\/10401230209149099","volume":"14","author":"R Tandon","year":"2002","unstructured":"Tandon R, Jibson MD (2002) Extrapyramidal side effects of antipsychotic treatment: scope of problem and impact on outcome. Ann Clin Psychiatry 14:123\u2013129","journal-title":"Ann Clin Psychiatry"},{"key":"1757_CR107","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1001\/jama.281.4.341","volume":"281","author":"CM Tanner","year":"1999","unstructured":"Tanner CM, Ottman R, Goldman SM, Ellenberg J, Chan P, Mayeux R, Langston JW (1999) Parkinson disease in twins: an etiologic study. JAMA 281:341\u2013346","journal-title":"JAMA"},{"issue":"2","key":"1757_CR108","doi-asserted-by":"crossref","first-page":"R183","DOI":"10.1093\/hmg\/ddm159","volume":"16","author":"B Thomas","year":"2007","unstructured":"Thomas B, Beal MF (2007) Parkinson\u2019s disease. Hum Mol Genet 16(2):R183\u2013R194","journal-title":"Hum Mol Genet"},{"key":"1757_CR109","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/978-3-211-73574-9_8","volume":"72","author":"F Tribl","year":"2007","unstructured":"Tribl F, Arzberger T, Riederer P, Gerlach M (2007) Tyrosinase is not detected in human catecholaminergic neurons by immunohistochemistry and Western blot analysis. J Neural Transm Suppl 72:51\u201355","journal-title":"J Neural Transm Suppl"},{"key":"1757_CR110","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s10633-005-7349-6","volume":"110","author":"R Tzekov","year":"2005","unstructured":"Tzekov R (2005) Ocular toxicity due to chloroquine and hydroxychloroquine: electrophysiological and visual function correlates. Doc Ophthalmol 110:111\u2013120","journal-title":"Doc Ophthalmol"},{"key":"1757_CR111","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12974-014-0228-x","volume":"12","author":"N Viceconte","year":"2015","unstructured":"Viceconte N, Burguillos MA, Herrera AJ, De Pablos RM, Joseph B, Venero JL (2015) Neuromelanin activates proinflammatory microglia through a caspase-8-dependent mechanism. J Neuroinflamm 12:5","journal-title":"J Neuroinflamm"},{"key":"1757_CR112","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1046\/j.1471-4159.2003.01917.x","volume":"86","author":"K Wakamatsu","year":"2003","unstructured":"Wakamatsu K, Fujikawa K, Zucca FA, Zecca L, Ito S (2003) The structure of neuromelanin as studied by chemical degradative methods. J Neurochem 86:1015\u20131023","journal-title":"J Neurochem"},{"key":"1757_CR113","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1755-148X.2007.00415.x","volume":"21","author":"K Wakamatsu","year":"2008","unstructured":"Wakamatsu K, Hu DN, McCormick SA, Ito S (2008) Characterization of melanin in human iridal and choroidal melanocytes from eyes with various colored irides. Pigment Cell Melanoma Res 21:97\u2013105","journal-title":"Pigment Cell Melanoma Res"},{"key":"1757_CR114","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1111\/jnc.13237","volume":"135","author":"K Wakamatsu","year":"2015","unstructured":"Wakamatsu K, Tabuchi K, Ojika M, Zucca FA, Zecca L, Ito S (2015) Norepinephrine and its metabolites are involved in the synthesis of neuromelanin derived from the locus coeruleus. J Neurochem 135:768\u2013776","journal-title":"J Neurochem"},{"key":"1757_CR115","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/BF02860136","volume":"17","author":"MG Whiting","year":"1963","unstructured":"Whiting MG (1963) Toxicity of cycads. Econ Bot 17:271\u2013302","journal-title":"Econ Bot"},{"key":"1757_CR116","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1096\/fj.02-0314fje","volume":"17","author":"H Wilms","year":"2003","unstructured":"Wilms H, Rosenstiel P, Sievers J, Deuschl G, Zecca L, Lucius R (2003) Activation of microglia by human neuromelanin is NF-kappaB dependent and involves p38 mitogen-activated protein kinase: implications for Parkinson\u2019s disease. FASEB J 17:500\u2013502","journal-title":"FASEB J"},{"key":"1757_CR117","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1016\/j.neurobiolaging.2007.04.009","volume":"29","author":"K Wirdefeldt","year":"2008","unstructured":"Wirdefeldt K, Gatz M, Bakaysa SL et al (2008) Complete ascertainment of Parkinson disease in the Swedish twin registry. Neurobiol Aging 29:1765\u20131773","journal-title":"Neurobiol Aging"},{"key":"1757_CR118","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.3390\/biom5021122","volume":"5","author":"S Xu","year":"2015","unstructured":"Xu S, Chan P (2015) Interaction between Neuromelanin and Alpha-Synuclein in Parkinson\u2019s Disease. Biomolecules 5:1122\u20131142","journal-title":"Biomolecules"},{"key":"1757_CR119","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1007\/s00702-011-0636-3","volume":"118","author":"Q Xuan","year":"2011","unstructured":"Xuan Q, Xu SL, Lu DH, Yu S, Zhou M, Ueda K, Cui YQ, Zhang BY, Chan P (2011) Increased expression of alpha-synuclein in aged human brain associated with neuromelanin accumulation. J Neural Transm 118:1575\u20131583","journal-title":"J Neural Transm"},{"key":"1757_CR120","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1001\/archneur.60.3.337","volume":"60","author":"C Zarow","year":"2003","unstructured":"Zarow C, Lyness SA, Mortimer JA, Chui HC (2003) Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch Neurol 60:337\u2013341","journal-title":"Arch Neurol"},{"key":"1757_CR121","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/S0014-5793(01)03269-0","volume":"510","author":"L Zecca","year":"2002","unstructured":"Zecca L, Fariello R, Riederer P, Sulzer D, Gatti A, Tampellini D (2002) The absolute concentration of nigral neuromelanin, assayed by a new sensitive method, increases throughout the life and is dramatically decreased in Parkinson\u2019s disease. FEBS Lett 510:216\u2013220","journal-title":"FEBS Lett"},{"key":"1757_CR122","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.tins.2003.08.009","volume":"26","author":"L Zecca","year":"2003","unstructured":"Zecca L, Zucca FA, Wilms H, Sulzer D (2003) Neuromelanin of the substantia nigra: a neuronal black hole with protective and toxic characteristics. Trends Neurosci 26:578\u2013580","journal-title":"Trends Neurosci"},{"key":"1757_CR123","doi-asserted-by":"crossref","first-page":"17567","DOI":"10.1073\/pnas.0808768105","volume":"105","author":"L Zecca","year":"2008","unstructured":"Zecca L, Bellei C, Costi P et al (2008a) New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals. Proc Natl Acad Sci USA 105:17567\u201317572","journal-title":"Proc Natl Acad Sci USA"},{"key":"1757_CR124","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00401-008-0361-7","volume":"116","author":"L Zecca","year":"2008","unstructured":"Zecca L, Wilms H, Geick S et al (2008b) Human neuromelanin induces neuroinflammation and neurodegeneration in the rat substantia nigra: implications for Parkinson\u2019s disease. Acta Neuropathol 116:47\u201355","journal-title":"Acta Neuropathol"},{"issue":"1","key":"1757_CR125","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s12640-009-9140-z","volume":"19","author":"W Zhang","year":"2011","unstructured":"Zhang W, Phillips K, Wielgus AR, Liu J, Albertini A, Zucca FA, Faust R, Qian SY, Miller DS, Chignell CF, Wilson B, Jackson-Lewis V, Przedborski S, Joset D, Loike J, Hong JS, Sulzer D, Zecca L (2011) Neuromelanin activates microglia and induces degeneration of dopaminergic neurons: implications for progression of Parkinson's disease. Neurotox Res 19(1):63-72. doi: 10.1007\/s12640-009-9140-z","journal-title":"Neurotox Res"},{"key":"1757_CR126","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2741\/E591","volume":"5","author":"W Zhang","year":"2013","unstructured":"Zhang W, Zecca L, Wilson B, Ren HW, Wang YJ, Wang XM, Hong JS (2013) Human neuromelanin: an endogenous microglial activator for dopaminergic neuron death. Front Biosci (Elite Ed) 5:1\u201311","journal-title":"Front Biosci (Elite Ed)"},{"key":"1757_CR127","doi-asserted-by":"crossref","first-page":"5063","DOI":"10.1002\/adma.201502201","volume":"27","author":"R Zhang","year":"2015","unstructured":"Zhang R, Fan Q, Yang M, Cheng K, Lu X, Zhang L, Huang W, Cheng Z (2015) Engineering melanin nanoparticles as an efficient drug-delivery system for imaging-guided chemotherapy. Adv Mater 27:5063\u20135069","journal-title":"Adv Mater"},{"key":"1757_CR128","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S0006-8993(01)03292-9","volume":"926","author":"W Zhou","year":"2002","unstructured":"Zhou W, Schaack J, Zawada WM, Freed CR (2002) Overexpression of human alpha-synuclein causes dopamine neuron death in primary human mesencephalic culture. Brain Res 926:42\u201350","journal-title":"Brain Res"},{"key":"1757_CR129","doi-asserted-by":"publisher","unstructured":"Zucca FA, Segura-Aguilar J, Ferrari E, Mu\u00f1oz P, Paris I, Sulzer D, Sarna T, Casella L, Zecca L (2015) Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson's disease. Prog Neurobiol. doi: 10.1016\/j.pneurobio.2015.09.012","DOI":"10.1016\/j.pneurobio.2015.09.012"}],"container-title":["Archives of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-016-1757-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00204-016-1757-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-016-1757-0","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T16:54:56Z","timestamp":1568048096000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00204-016-1757-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,16]]},"references-count":129,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["1757"],"URL":"https:\/\/doi.org\/10.1007\/s00204-016-1757-0","relation":{},"ISSN":["0340-5761","1432-0738"],"issn-type":[{"value":"0340-5761","type":"print"},{"value":"1432-0738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,16]]}}}