Abstract
Dark pigmented organelles, present in catecholaminergic neurons in specific brain regions, are indicated with the term neuromelanin (NM). They are complex structures, mainly comprised by granules of melanin polymer, closely associated with peptide and lipid components. Although NM is present in several animals, it is considered as a unique feature of the man due to the extremely higher degree of pigmentation, even in comparison to other primates. For a long time NM was considered an inert cellular waste product of poor interest that in the absence of mechanism of removal accumulates during the entire lifespan. Just recently, NM has received renewed attention for its role in Parkinson’s disease (PD), where a selective death of the NM-containing neurons of the substantia nigra (SN) pars compacta is observed, while nonpigmented neurons are mostly spared. A physiological accumulation of NM seems to be a protective phenomenon, which prevents several neurotoxic processes. In particular, in dopaminergic neurons of SN, where no ferritin has been detected, NM appears to function as an iron storage system. However, in PD patients NM released by dying neurons can trigger a vicious circle of neuroinflammation and ensuing neuronal death. This chapter presents the structure, the production, and the development of NM, as well as the recent hypotheses about physiological NM role and its behavior in pathological conditions.
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Abbreviations
- 4-AHPEA:
-
4-amino-3-hydroxyphenylethylamine
- AFM:
-
Atomic force microscopy
- DA:
-
Dopamine
- DAQ:
-
Dopaminoquinone
- DOPA:
-
Dihydroxyphenylalanine
- DQ:
-
DOPA-quinone
- FEL:
-
Free-electron laser
- NM:
-
Neuromelanin
- PD:
-
Parkinson’s disease
- PDCA:
-
Pyrrole-2,3-dicarboxylic acid
- PEEM:
-
Photoelectron emission microscopy
- PTCA:
-
Pyrrole-2,3,5-tricarboxylic acid
- RNS:
-
Reactive nitrogen species
- ROS:
-
Reactive oxygen species
- SEM:
-
Scanning electron microscopy
- SN:
-
Substantia nigra
- TDCA:
-
Thiazole-4,5-dicarboxylic acid
- TTCA:
-
Thiazole-2,4,5-tricarboxylic acid
References
Adler, A. (1939). Melanin pigment in the central nervous system of vertebrates. The Journal of Comparative Neurology, 70, 315–329.
Adler, A. (1942). Melanin pigment in the brain of the gorilla. The Journal of Comparative Neurology, 76, 501–507.
Agrup, G., Hansson, C., Rorsman, H., & Rosengren, E. (1982). The effect of cysteine on oxidation of tyrosine, dopa, and cysteinyldopas. Archives of Dermatological Research, 272, 103–115.
Andersson, M., Appelkvist, E. L., Kristensson, K., & Dallner, G. (1987). Distribution of dolichol and dolichyl phosphate in human brain. Journal of Neurochemistry, 49, 685–691.
Bazelon, M., Fenichel, G. M., & Randall, J. (1967). Studies on Neuromelanin. I. A melanin system in the human adult brainstem. Neurology, 17, 512–519.
Bliss, J. M., Ford, D., Swerdlow, A. J., Armstrong, B. K., Cristofolini, M., Elwood, J. M., Green, A., Holly, E. A., Mack, T., Mackie, R. M., Osterlind, A., Walter, S. D., Peto, J., & Easton, D. F. (1995). Risk of cutaneous melanoma associated with pigmentation characteristics and freckling: Systematic overview of 10 case–control studies. International Journal of Cancer, 62, 367–376.
Bogerts, B. (1981). A brainstem atlas of catecholaminergic neurons in man, using melanin as a natural marker. The Journal of Comparative Neurology, 197, 63–80.
Braak, H., Del Tredici, K., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003). Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of Aging, 24, 197–211.
Bridelli, M. G., Tampellini, D., & Zecca, L. (1999). The structure of neuromelanin and its iron binding site studied by infrared spectroscopy. FEBS Letters, 457, 8–22.
Brown, J. O. (1943). Pigmentation in the substantia nigra and locus coeruleus in certain carnivores. The Journal of Comparative Neurology, 79, 393–405.
Bush, W. D., Garguilo, J., Zucca, F. A., Albertini, A., Zecca, L., Edwards, G. S., Nemanich, R. J., & Simon, J. D. (2006). The surface oxidation potential of human neuromelanin reveals a spherical architecture with a pheomelanin core and a eumelanin surface. Proceedings of the National Academy of Sciences USA, 103, 14785–14789.
Calne, D. B., Snow, B. J., & Lee, C. (1992). Criteria for diagnosing Parkinson’s disease. Annals of Neurology, 32(Suppl), 125–127.
Chen, H., Zhang, S. M., Hernán, M. A., Schwarzschild, M. A., Willett, W. C., Colditz, G. A., Speizer, F. E., & Ascherio, A. (2003). Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Archives of Neurology, 60, 1059–1064.
Crippa, P. R., Eisner, M., Morante, S., Stellato, F., Vicentin, F. C., & Zecca, L. (2010). An XAS study of the sulfur environment in human neuromelanin and its synthetic analogs. European Biophysics Journal, 39, 959–970.
D’Amato, R. J., Lipman, Z. P., & Snyder, S. H. (1986). Selectivity of the parkinsonian neurotoxin MPTP: Toxic metabolite MPP+ binds to neuromelanin. Science, 231, 987–989.
Dedov, V. N., Griffiths, F. M., Garner, B., Halliday, G. M., & Double, K. L. (2007). Lipid content determines aggregation of neuromelanin granules in vitro. Journal of Neural Transmission, 72(Suppl), 35–38.
Dexter, D. T., Carter, C. J., Wells, F. R., Javoy-Agid, F., Agid, Y., Lees, A., Jenner, P., & Marsden, C. D. (1989). Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. Journal of Neurochemistry, 52, 381–389.
Double, K. L. (2012). Neuronal vulnerability in Parkinson’s disease. Parkinsonism & Related Disorders, 18(Suppl 1), 52–54.
Double, K. L., Zecca, L., Costi, P., Mauer, M., Griesinger, C., Ito, S., Ben-Shachar, D., Bringmann, G., Fariello, R. G., Riederer, P., & Gerlach, M. (2000). Structural characteristics of human substantia nigra neuromelanin and synthetic dopamine melanins. Journal of Neurochemistry, 75, 2583–2589.
Double, K. L., Gerlach, M., Schunemann, V., Trautwein, A. X., Zecca, L., Gallorini, M., Youdim, M. B., Riederer, P., & Ben-Shachar, D. (2003). Iron-binding characteristics of neuromelanin of the human substantia nigra. Biochemical Pharmacology, 66, 489–494.
Double, K. L., Dedov, V. N., Fedorow, H., Kettle, E., Halliday, G. M., Garner, B., & Brunk, U. T. (2008). The comparative biology of neuromelanin and lipofuscin in the human brain. Cellular and Molecular Life Sciences, 65, 1669–1682.
Duffy, P. E., & Tennyson, V. M. (1965). Phase and electron microscopic observations of lewy bodies and melanin granules in the substantia nigra and locus coeruleus in Parkinson’s disease. Journal of Neuropathology and Experimental Neurology, 24, 398–414.
Fasano, M., Bergamasco, B., & Lopiano, L. (2006). Is neuromelanin changed in Parkinson’s disease? Investigations by magnetic spectroscopies. Journal of Neural Transmission, 113, 769–774.
Faucheux, B. A., Martin, M. E., Beaumont, C., Hauw, J. J., Agid, Y., & Hirsch, E. C. (2003). Neuromelanin associated redox-active iron is increased in the substantia nigra of patients with Parkinson’s disease. Journal of Neurochemistry, 86, 1142–1148.
Fedorow, H., Tribl, F., Halliday, G., Gerlach, M., Riederer, P., & Double, K. L. (2005a). Neuromelanin in human dopamine neurons: Comparison with peripheral melanins and relevance to Parkinson’s disease. Progress in Neurobiology, 75, 109–124.
Fedorow, H., Pickford, R., Hook, J., Double, K. L., Halliday, G. M., Gerlach, M., Riederer, P., & Garner, B. (2005b). Dolichol is the major lipid in human substantia nigra neuromelanin. Journal of Neurochemistry, 92, 990–995.
Fedorow, H., Pickford, R., Kettle, E., Cartwright, M., Halliday, G. M., Gerlach, M., Riederer, P., Garner, B., & Double, K. L. (2006). Investigation of the lipid component of neuromelanin. Journal of Neural Transmission, 113, 735–739.
Foley, J. M., & Baxter, D. (1958). On the nature of pigment granules in the cell of the locus coeruleus and substantia nigra. Journal of Neuropathology and Experimental Neurology, 17, 586–598.
Gao, X., Simon, K. C., Han, J., Schwarzschild, M. A., & Ascherio, A. (2009). Genetic determinants of hair color and Parkinson’s disease. Annals of Neurology, 65, 76–82.
Gao, H. M., Zhou, H., Zhang, F., Wilson, B. C., Kam, W., & Hong, J. S. (2011). HMGB1 acts on microglia Mac1 to mediate chronic neuroinflammation that drives progressive neurodegeneration. The Journal of Neuroscience, 31, 1081–1092.
Gaspar, P., Berger, B., Gay, M., Hamon, M., Cesselin, F., Vighy, A., Javoy-Agid, F., & Agid, Y. (1983). Tyrosine hydroxylase and methionine-enkephalin in the human mesencephalon: Immunocytochemical localization and relationships. Journal of the Neurological Sciences, 58, 247–267.
Gelb, J. D., Oliver, E., & Gilman, S. (1999). Diagnostic criteria for Parkinson disease. Archives of Neurology, 56, 33–39.
Gerlach, M., Trautwein, A. X., Zecca, L., Youdim, M. B. H., & Riederer, P. (1995). Mossbauer spectroscopic studies of purified human neuromelanin isolated from the substantia nigra. Journal of Neurochemistry, 65, 923–926.
Gillilan, L. A. (1943). The nuclear pattern of the non-tectal portions of the midbrain and isthmus in Ungulates. The Journal of Comparative Neurology, 78, 289–364.
Graham, D. G. (1979). On the origin and significance of neuromelanin. Archives of Pathology & Laboratory Medicine, 103, 359–362.
Greco, G., Panzella, L., Gentile, G., Errico, M. E., Carfagna, C., Napolitano, A., & D’Ischia, M. (2011). A melanin-inspired pro-oxidant system for dopa(mine) polymerization: Mimicking the natural casing process. Chemical Communications, 47, 10308–10310.
Halliday, G. M., Ophof, A., Broe, M., Jensen, P. H., Kettle, E., Fedorow, H., Cartwright, M. I., Griffiths, F. M., Shepherd, C. E., & Double, K. L. (2005). α-Synuclein redistributes to neuromelanin lipid in the substantia nigra early in Parkinson’s disease. Brain, 128, 2654–2664.
Halliday, G., Fedorow, H., Rickert, C. H., Gerlach, M., Riederer, P., & Double, K. L. (2006). Evidence for specific phases in the development of human neuromelanin. Journal of Neural Transmission, 113, 721–728.
Hirosawa, K. (1968). Electron microscopic studies on pigment granules in the substantia nigra and locus coeruleus of the Japanese monkey (Macaca fuscata yakui). Zeitschrift für Zellforschung und Mikroskopische Anatomie, 88, 187–203.
Ikemoto, K., Nagatsu, I., Ito, S., King, R. A., Nishimura, A., & Nagatsu, T. (1998). Does tyrosinase exist in neuromelanin-pigmented neurons in the human substantia nigra? Neuroscience Letters, 253, 198–200.
Ito, S. (2003). A chemist’s view of melanogenesis. Pigment Cell Research, 16, 230–236.
Ito, S. (2006). Encapsulation of a reactive core in neuromelanin. Proceedings of the National Academy of Sciences USA, 103, 14647–14648.
Ito, S., & Wakamatsu, K. (2003). Quantitative analysis of eumelanin and pheomelanin in humans, mice, and other animals: A comparative study. Pigment Cell Research, 16, 523–531.
Ito, S., & Wakamatsu, K. (2006). Chemistry of melanins. In J. J. Nordlund, R. E. Boissy, V. J. Hearing, R. A. King, W. S. Oetting, & J. P. Ortonne (Eds.), The pigmentary system: Physiology and pathophysiology (pp. 282–310). Blackwell.
Ito, S., Kato, T., & Fujita, K. (1988). Covalent binding of catechols to proteins through the sulphydryl group. Biochemical Pharmacology, 37, 1707–1710.
Kin, N. M. K., Palo, J., Haltia, M., & Wolfe, L. S. (1983). High levels of brain dolichols in neuronal ceroid-lipofuscinosis and senescence. Journal of Neurochemistry, 40, 1465–1473.
Korner, A., & Pawelek, J. (1982). Mammalian tyrosinase catalyzes three reactions in the biosynthesis of melanin. Science, 217, 1163–1165.
Land, E. J., Ito, S., Wakamatsu, K., & Riley, P. A. (2003). Rate constants for the first two chemical steps of eumelanogenesis. Pigment Cell Research, 16, 487–493.
Lindquist, N. G., Larsson, B. S., & Lyden-Sokolowski, A. (1988). Autoradiography of [14C]paraquat or [14C]diquat in frogs and mice: Accumulation in neuromelanin. Neuroscience Letters, 93, 1–6.
Liu, Y., & Simon, J. D. (2003). Isolation and biophysical studies of natural eumelanins: Applications of imaging technologies and ultrafast spectroscopy. Pigment Cell Research, 16, 606–618.
Liu, Y., Hong, L., Kempf, V. R., Wakamatsu, K., Ito, S., & Simon, J. D. (2004). Ion-exchange and adsorption of Fe(III) by Sepia melanin. Pigment Cell Research, 17, 262–269.
Mann, D. M., & Yates, P. O. (1983). Possible role of neuromelanin in the pathogenesis of Parkinson’s disease. Mechanisms of Ageing and Development, 21, 193–203.
Mann, D. M., Yates, P. O., & Barton, C. M. (1977). Neuromelanin and RNA in cells of substantia nigra. Journal of Neuropathology and Experimental Neurology, 36, 379–383.
Mårs, U., & Larsson, B. S. (1999). Pheomelanin is a binding site for drugs and chemicals. Pigment Cell Research, 12, 266–272.
Marsden, C. D. (1961). Pigmentation in the nucleus substantiae nigrae of mammals. Journal of Anatomy, 95, 256–261.
Matsunaga, J., Sinha, D., Pannell, L., Santis, C., Solano, F., Wistow, G. J., & Hearing, V. J. (1999). Enzyme activity of macrophage migration inhibitory factor toward oxidized catecholamines. The Journal of Biological Chemistry, 274, 3268–3271.
Moos, T. (2000). Absence of ferritin protein in substantia nigra pars compacta neurons. A reappraisal to the role of iron in Parkinson’s disease pathogenesis. Movement Disorders, 15(Suppl 3), 319A.
Moses, H. L., Ganote, C. E., Beaver, D. L., & Schuffman, S. S. (1966). Light and electron microscopic studies of pigment in human and rhesus monkey substantia nigra and locus coeruleus. The Anatomical Record, 155, 167–383.
Okun, M. R. (1997). The role of peroxidase in neuromelanin synthesis: A review. Physiological Chemistry and Physics and Medical NMR, 29, 15–22.
Ostergren, A., Annas, A., Skog, K., Lindquist, N. G., & Brittebo, E. B. (2004). Long-term retention of neurotoxic beta-carbolines in brain neuromelanin. Journal of Neural Transmission, 111, 141–157.
Paris, I., Perez-Pastene, C., Cardenas, S., Iturra, P., Munõz, P., Couve, E., Caviedes, P., & Segura-Aguilar, J. (2010). Aminochrome induces disruption of actin, alpha-, and beta-tubulin cytoskeleton networks in substantia-nigra-derived cell line. Neurotoxicity Research, 18, 82–92.
Prota, G. (1992). Melanin and melanogenesis. Academic.
Pullarkat, R. K., & Reha, H. (1982). Accumulation of dolichols in brains of elderly. The Journal of Biological Chemistry, 257, 5991–5993.
Rosengren, E., Linder-Eliasson, E., & Carlsson, A. (1985). Detection of 5-S-cysteinyldopamine in human brain. Journal of Neural Transmission, 63, 247–253.
Salazar, M., Sokoloski, T. D., & Patil, P. N. (1978). Binding of dopaminergic drugs by the neuromelanin of the substantia nigra, synthetic melanins and melanin granules. Federation Proceedings, 37, 2403–2407.
Samokhvalov, A., Hong, L., Liu, Y., Garguilo, J., Nemanich, R. J., Edwards, G. S., & Simon, J. D. (2005). Oxidation potentials of human eumelanosomes and pheomelanosomes. Photochemistry and Photobiology, 81, 145–148.
Scherer, H. J. (1939). Melanin pigmentation of the substantia nigra in primates. The Journal of Comparative Neurology, 71, 91–98.
Shima, T., Sarna, T., Swartz, H. M., Stroppolo, A., Gerbasi, R., & Zecca, L. (1997). Binding of iron to neuromelanin of human substantia nigra and synthetic melanin: An electron paramagnetic resonance spectroscopy study. Free Radical Biology & Medicine, 23, 110–119.
Simon, J. D., & Peles, D. N. (2010). The red and the black. Accounts of Chemical Research, 43, 1452–1460.
Simon, J. D., Peles, D., Wakamatsu, K., & Ito, S. (2009). Current challenges in understanding melanogenesis: Bridging chemistry, biological control, morphology, and function. Pigment Cell & Melanoma Research, 22, 563–579.
Spencer, J. P. E., Jenner, P., Daniel, S. E., Lees, A. J., Marsden, D. C., & Halliwell, B. (1998). Conjugates of catecholamines with cysteine and GSH in Parkinson’s disease: Possible mechanism of formation involving reactive oxygen species. Journal of Neurochemistry, 71, 2112–2122.
Sulzer, D., Bogulavsky, J., Larsen, K. E., Behr, G., Karatekin, E., Kleinman, M. H., Turro, N., Krantzi, D., Edwardsi, R. H., Greene, L. A., & Zecca, L. (2000). Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles. Proceedings of the National Academy of Sciences USA, 97, 11869–11874.
Thody, A. J., Higgins, E. M., Wakamatsu, K., Ito, S., Burchill, S. A., & Marks, J. M. (1991). Pheomelanin as well as eumelanin is present in human epidermis. The Journal of Investigative Dermatology, 97, 340–344.
Tribl, F., Gerlach, M., Marcus, K., Asan, E., Tatschner, T., Arzberger, T., Meyer, H. E., Bringmann, G., & Riederer, P. (2005). “Subcellular proteomics” of neuromelanin granules isolated from the human brain. Molecular & Cellular Proteomics, 4, 945–957.
Tse, D. C. S., McCreery, R. L., & Adams, R. N. (1976). Potential oxidative pathways of brain catecholamines. Journal of Medicinal Chemistry, 19, 37–40.
Varki, A., Cummings, R., Esko, J., Freeze, H., Hart, G., & Marth, J. (1999). Essentials of glycobiology. Cold Spring Harbor Laboratory Press.
Vincensi, M. R., D’Ischia, M., Napolitano, A., Procaccini, E. M., Riccio, G., Monfrecola, G., Santoianni, P., & Prota, G. (1998). Pheomelanin versus eumelanin as a chemical indicator of ultraviolet sensitivity in fair-skinned subjects at high risk for melanoma: A pilot study. Melanoma Research, 8, 53–58.
Wakamatsu, K., Fujikawa, K., Zucca, F. A., Zecca, L., & Ito, S. (2003). The structure of neuromelanin as studied by chemical degradative methods. Journal of Neurochemistry, 86, 1015–1023.
Ward, W. C., Guan, Z., Zucca, F. A., Fariello, R. G., Kordestani, R., Zecca, L., Raetz, C. R. H., & Simon, J. D. (2007). Identification and quantification of dolichol and dolichoic acid in neuromelanin from substantia nigra of the human brain. Journal of Lipid Research, 48, 1457–1462.
Wu, D. C., Jackson-Lewis, V., Vila, M., Tieu, K., Teismann, P., Vadseth, C., Choi, D. K., Ischiropoulos, H., & Przedborski, S. (2002). Blockade of microglial activation is neuroprotective in the 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. The Journal of Neuroscience, 22, 1763–1771.
Ye, T., Hong, L., Garguilo, J., Pawlak, A., Edwards, G. S., Nemanich, R. J., Sarna, T., & Simon, J. D. (2006). Photoionization thresholds of melanins obtained from free electron laser-photoelectron emission microscopy, femtosecond transient absorption spectroscopy and electron paramagnetic resonance measurements of oxygen consumption. Photochemistry and Photobiology, 82, 733–737.
Young, T. E., & Babbitt, B. W. (1983). Electrochemical study of the oxidation of α-methyldopamine, α-methylnoradrenaline, and dopamine. The Journal of Organic Chemistry, 48, 562–566.
Zareba, M., Bober, A., Korytowski, W., Zecca, L., & Sarna, T. (1995). The effect of a synthetic neuromelanin on yield of free hydroxyl radicals generated in model systems. Biochimica et Biophysica Acta, 1271, 343–348.
Zecca, L., & Swartz, H. M. (1993). Total and paramagnetic metals in human substantia nigra and its neuromelanin. Journal of Neural Transmission. Parkinson’s Disease and Dementia Section, 5, 203–213.
Zecca, L., Costi, P., Mecacci, C., Ito, S., Terreni, M., & Sonnino, S. (2000). Interaction of human substantia nigra neuromelanin with lipids and peptides. Journal of Neurochemistry, 74, 1758–1765.
Zecca, L., Tampellini, D., Gerlach, M., Riederer, P., Fariello, R. G., & Sulzer, D. (2001a). Substantia nigra neuromelanin: Structure, synthesis, and molecular behaviour. Molecular Pathology, 54, 414–418.
Zecca, L., Gallorini, M., Schunemann, V., Trautwein, A. X., Gerlach, M., Riederer, P., Vezzoni, P., & Tampellini, D. (2001b). Iron, neuromelanin and ferritin content in the substantia nigra of normal subjects at different ages: Consequences for iron storage and neurodegenerative processes. Journal of Neurochemistry, 76, 1766–1773.
Zecca, L., Fariello, R., Riederer, P., Sulzer, D., Gatti, A., & Tampellini, D. (2002a). The absolute concentration of nigral neuromelanin, assayed by a new sensitive method, increases throughout the life and is dramatically decreased in Parkinson’s disease. FEBS Letters, 510, 216–220.
Zecca, L., Tampellini, D., Gatti, A., Crippa, R., Eisner, M., Sulzer, D., Ito, S., Fariello, R., & Gallorini, M. (2002b). The neuromelanin of human substantia nigra and its interaction with metals. Journal of Neural Transmission, 109, 663–672.
Zecca, L., Stroppolo, A., Gatti, A., Tampellini, D., Toscani, M., Gallorini, M., Giaveri, G., Arosio, P., Santambrogio, P., Fariello, R. G., Karatekin, E., Kleinman, M. H., Turro, N. J., Hornykiewicz, O., & Zucca, F. A. (2004). The role of iron and copper molecules in the neuronal vulnerability of locus coeruleus and substantia nigra during aging. Proceedings of the National Academy of Sciences USA, 101, 9843–9848.
Zecca, L., Bellei, C., Costi, P., Albertini, A., Monzani, E., Casella, L., Gallorini, M., Bergamaschi, L., Moscatelli, A., Turro, N. J., Eisner, M., Crippa, P. R., Ito, S., Wakamatsu, K., Bush, W. D., Ward, W. C., Simon, J. D., & Zucca, F. A. (2008). New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals. Proceedings of the National Academy of Sciences USA, 105, 17567–17572.
Zhang, F., & Dryhurst, G. (1994). Effects of L-cysteine on the oxidation chemistry of dopamine: New reaction pathways of potential relevance to idiopathic Parkinson’s disease. Journal of Medicinal Chemistry, 37, 1084–1098.
Zhang, W., Phillips, K., Wielgus, A. R., Liu, J., Albertini, A., Zucca, F. A., Faust, R., Qian, S. Y., Miller, D. S., Chingell, C. F., Wilson, B., Jackson-Lewis, V., Przedborski, S., Joset, D., Loike, J., Hong, J. S., Sulzer, D., & Zecca, L. (2011). Neuromelanin activates microglia and induces degeneration of dopaminergic neurons: Implications for progression of Parkinson’s disease. Neurotoxicity Research, 19, 63–72.
Zhou, G. P., & Troy, F. A. (2004). NMR Study of the preferred membrane orientation of polyisoprenols (Dolichol) and the impact of their complex with polyisoprenyl recognition sequence peptides on membrane structure. Glycobiology, 15, 347–359.
Zucca, F. A., Giaveri, G., Gallorini, M., Albertini, A., Toscani, M., Pezzoli, G., Lucius, R., Willms, H., Sulzer, D., Ito, S., Wakamatsu, K., & Zecca, L. (2004). The neuromelanin of human substantia nigra: Physiological and pathogenic aspects. Pigment Cell Research, 17, 610–617.
Acknowledgments
This work was financially supported by the HWP-Program “Chancengleichheit für Frauen in Forschung und Lehre,” TU München and the Foundation Blanceflor Boncompagni-Ludovisi, neÕ Bildt. N. Vona is gratefully acknowledged for assistance preparing the figures.
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Greco, G. (2022). Neuromelanin and Parkinson’s Disease. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-031-15080-7_12
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