{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:05:06Z","timestamp":1791115506985,"version":"4.1.0"},"reference-count":162,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2015,6,5]],"date-time":"2015-06-05T00:00:00Z","timestamp":1433462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Natural Science Foundation","award":["81171298"],"award-info":[{"award-number":["81171298"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a very common neurodegenerative disorder characterized by the accumulation of \u03b1-synuclein (\u03b1-syn) into Lewy body (LB) inclusions and the loss of neuronmelanin (NM) containing dopamine (DA) neurons in the substantia nigra (SN). Pathological \u03b1-syn and NM are two prominent hallmarks in this selective and progressive neurodegenerative disease. Pathological \u03b1-syn can induce dopaminergic neuron death by various mechanisms, such as inducing oxidative stress and inhibiting protein degradation systems. Therefore, to explore the factors that trigger \u03b1-syn to convert from a non-toxic protein to toxic one is a pivotal question to clarify the mechanisms of PD pathogenesis. Many triggers for pathological \u03b1-syn aggregation have been identified, including missense mutations in the \u03b1-syn gene, higher concentration, and posttranslational modifications of \u03b1-Syn. Recently, the role of NM in inducing \u03b1-syn expression and aggregation has been suggested as a mechanism for this pigment to modulate neuronal vulnerability in PD. NM may be responsible for PD and age-associated increase and aggregation in \u03b1-syn. Here, we reviewed our previous study and other recent findings in the area of interaction between NM and \u03b1-syn.<\/jats:p>","DOI":"10.3390\/biom5021122","type":"journal-article","created":{"date-parts":[[2015,6,5]],"date-time":"2015-06-05T10:23:07Z","timestamp":1433499787000},"page":"1122-1142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Interaction between Neuromelanin and Alpha-Synuclein in Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"5","author":[{"given":"Shengli","family":"Xu","sequence":"first","affiliation":[{"name":"Beijing Institute of Geriatrics, Xuanwu Hospital of Capital University of Medical Sciences,  No.45 changchun St., Xicheng District, Beijing 100053, China"},{"name":"Parkinson's disease Center of Beijing Institute for Brain Disorders, Beijing 100053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piu","family":"Chan","sequence":"additional","affiliation":[{"name":"Beijing Institute of Geriatrics, Xuanwu Hospital of Capital University of Medical Sciences,  No.45 changchun St., Xicheng District, Beijing 100053, China"},{"name":"Parkinson's disease Center of Beijing Institute for Brain Disorders, Beijing 100053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev.neuro.22.1.123","article-title":"Etiology and pathogenesis of Parkinson\u2019s disease","volume":"22","author":"Olanow","year":"1999","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/mds.25095","article-title":"Neuronal vulnerability, pathogenesis, and Parkinson\u2019s disease","volume":"28","author":"Sulzer","year":"2013","journal-title":"Mov. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1602\/neurorx.1.1.139","article-title":"Neurodegeneration and neuroprotection in Parkinson disease","volume":"1","author":"Fahn","year":"2004","journal-title":"NeuroRx"},{"key":"ref_4","first-page":"229","article-title":"Levodopa in the treatment of Parkinson\u2019s disease: An old drug still going strong","volume":"7","author":"Poewe","year":"2010","journal-title":"Clin. Interv. Aging"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/mds.870120607","article-title":"Symptoms and duration of the prodromal phase in Parkinson\u2019s disease","volume":"12","author":"Gonera","year":"1997","journal-title":"Mov. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.parkreldis.2006.12.014","article-title":"Non-motor dysfunction in Parkinson\u2019s disease","volume":"13","author":"Ziemssen","year":"2007","journal-title":"Park. Relat. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s00702-013-0966-4","article-title":"Sleep and non-motor symptoms in Parkinson\u2019s disease","volume":"120","author":"Maass","year":"2013","journal-title":"J. Neural Transm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3233\/JPD-130175","article-title":"Parkinson\u2019s disease\u2014The debate on the clinical phenomenology, aetiology, pathology and pathogenesis","volume":"3","author":"Jenner","year":"2013","journal-title":"J. Parkinsons Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1126\/science.276.5321.2045","article-title":"Mutation in the alpha-synuclein gene identified in families with Parkinson\u2019s disease","volume":"276","author":"Polymeropoulos","year":"1997","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Singleton, A.B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., and Nussbaum, R. (2003). \u03b1-Synuclein locus triplication causes Parkinson\u2019s disease. Science.","DOI":"10.1126\/science.1090278"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.neuron.2004.11.005","article-title":"Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology","volume":"44","author":"Zimprich","year":"2004","journal-title":"Neuron"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.molmed.2011.05.003","article-title":"Exploring the link between glucocerebrosidase mutations and parkinsonism","volume":"17","author":"Westbroek","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S1353-8020(03)00016-6","article-title":"Autosomal recessive parkinsonism linked to parkin gene in a Tunisian family. Clinical, genetic and pathological study","volume":"9","author":"Larnaout","year":"2003","journal-title":"Park. Relat. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1126\/science.1077209","article-title":"Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism","volume":"299","author":"Bonifati","year":"2003","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1126\/science.1096284","article-title":"Hereditary early-onset Parkinson\u2019s disease caused by mutations in PINK1","volume":"304","author":"Valente","year":"2004","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/ng.642","article-title":"Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson\u2019s disease","volume":"42","author":"Hamza","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1086\/424492","article-title":"Linkage disequilibrium and association of MAPT H1 in Parkinson disease","volume":"75","author":"Skipper","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"26292","DOI":"10.1074\/jbc.273.41.26292","article-title":"Binding of alpha-synuclein to brain vesicles is abolished by familial Parkinson\u2019s disease mutation","volume":"273","author":"Jensen","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/ana.410430320","article-title":"Low frequency of alpha-synuclein mutations in familial Parkinson\u2019s disease","volume":"43","author":"Farrer","year":"1998","journal-title":"Ann. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/ana.10795","article-title":"The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia","volume":"55","author":"Zarranz","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1212\/WNL.0b013e31828727ba","article-title":"A novel \u03b1-synuclein missense mutation in Parkinson disease","volume":"80","author":"Proukakis","year":"2013","journal-title":"Neurology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s00401-013-1096-7","article-title":"\u03b1-Synucleinopathy associated with G51D SNCA mutation: A link between Parkinson\u2019s disease and multiple system atrophy?","volume":"125","author":"Kiely","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2180.e1","DOI":"10.1016\/j.neurobiolaging.2014.03.024","article-title":"Novel \u03b1-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson\u2019s disease-type pathology","volume":"35","author":"Pasanen","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.arr.2014.01.004","article-title":"Ageing and Parkinson\u2019s disease: Why is advancing age the biggest risk factor?","volume":"14","author":"Reeve","year":"2014","journal-title":"Ageing Res. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.pneurobio.2013.04.004","article-title":"Mitochondrial dysfunction and oxidative stress in Parkinson\u2019s disease","volume":"106\u2013107","author":"Subramaniam","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.neuron.2009.01.033","article-title":"Interplay between cytosolic dopamine, calcium, and alpha-synuclein cause selective death of substantia nigra neurons","volume":"62","author":"Mosharov","year":"2009","journal-title":"Neuron"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz, P., Huenchuguala, S., Paris, I., and Segura-Aguilar, J. (2012). Dopamine oxidation and autophagy. Park. Dis.","DOI":"10.1155\/2012\/920953"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/j.1471-4159.2008.05385.x","article-title":"Neuronal pigmented autophagic vacuoles: Lipofuscin, neuromelanin, and ceroid as macroautophagic responses during aging and disease","volume":"106","author":"Sulzer","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1007\/s00702-011-0636-3","article-title":"Increased expression of \u03b1-synuclein in aged human brain associated with neuromelanin accumulation","volume":"118","author":"Xuan","year":"2011","journal-title":"J. Neural Transm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s12640-009-9140-z","article-title":"Neuromelanin activates microglia and induces degeneration of dopaminergic neurons: Implications for progression of Parkinson\u2019s disease","volume":"19","author":"Zhang","year":"2011","journal-title":"Neurotox. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/S0140-6736(04)17103-1","article-title":"Alpha-synuclein locus duplication as a cause of familial Parkinson\u2019s disease","volume":"364","author":"Kachergus","year":"2004","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e26159","DOI":"10.1371\/journal.pone.0026159","article-title":"SNCA triplication Parkinson\u2019s patient\u2019s iPSC-derived DA neurons accumulate \u03b1-synuclein and are susceptible to oxidative stress","volume":"6","author":"Byers","year":"2011","journal-title":"PLoS ONE"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0306-4522(00)00077-4","article-title":"Enhanced viability to oxidative stress by alpha-synuclein mutations and C-terminal truncation","volume":"97","author":"Kanda","year":"2000","journal-title":"Neuroscience"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9843","DOI":"10.1074\/jbc.274.14.9843","article-title":"Both familial Parkinson\u2019s disease mutations accelerate alpha-synuclein aggregation","volume":"274","author":"Narhi","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"21856","DOI":"10.1074\/jbc.M114.553297","article-title":"The H50Q mutation enhances \u03b1-synuclein aggregation, secretion and toxicity","volume":"289","author":"Khalaf","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1111\/jnc.12806","article-title":"Divergent effects of the H50Q and G51D SNCA mutations on the aggregation of \u03b1-synuclein","volume":"131","author":"Rutherford","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6419","DOI":"10.1021\/bi5010365","article-title":"The newly discovered Parkinson\u2019s disease associated Finnish mutation (A53E) attenuates \u03b1-synuclein aggregation and membrane binding","volume":"53","author":"Ghosh","year":"2014","journal-title":"Biochemistry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s12035-014-8738-1","article-title":"Overexpression of human E46K mutant \u03b1-synuclein impairs macroautophagy via inactivation of JNK1-Bcl-2 pathway","volume":"50","author":"Yan","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"ref_39","first-page":"145","article-title":"Pathways to neurodegeneration: Mechanistic insights from GWAS in Alzheimer\u2019s disease, Parkinson\u2019s disease, and related disorders","volume":"18","author":"Ramanan","year":"2013","journal-title":"Am. J. Neurodegener. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1038\/ng.485","article-title":"Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson\u2019s disease","volume":"41","author":"Satake","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"\u03b1-Synuclein in Lewy bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"20288","DOI":"10.1074\/jbc.M710560200","article-title":"\u03b1-Synuclein protofibrils inhibit 26 S proteasome-mediated protein degradation: Understanding the cytotoxicity of protein protofibrils in neurodegenerative disease pathogenesis","volume":"283","author":"Zhang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_43","first-page":"19","article-title":"In vitro preparation of prefibrillar intermediates of amyloid-beta and alpha-synuclein","volume":"299","author":"Lashuel","year":"2005","journal-title":"Methods Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9678","DOI":"10.1074\/jbc.M409946200","article-title":"Metal-catalyzed oxidation of alpha-synuclein: Helping to define the relationship between oligomers, protofibrils, and filaments","volume":"280","author":"Cole","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/j.1440-1789.2007.00803.x","article-title":"The Lewy body in Parkinson\u2019s disease: Molecules implicated in the formation and degradation of alpha-synuclein aggregates","volume":"27","author":"Wakabayashi","year":"2007","journal-title":"Neuropathology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/jnc.12175","article-title":"Monoclonal antibodies selective for \u03b1-synuclein oligomers\/protofibrils recognize brain pathology in Lewy body disorders and \u03b1-synuclein transgenic mice with the disease-causing A30P mutation","volume":"126","author":"Fagerqvist","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"48976","DOI":"10.1074\/jbc.M208192200","article-title":"Characterization of cytoplasmic alpha-synuclein aggregates. Fibril formation is tightly linked to the inclusion-forming process in cells","volume":"277","author":"Lee","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.nbd.2014.05.009","article-title":"Immunotherapy targeting \u03b1-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P] \u03b1-synuclein mice","volume":"69","author":"Fagerqvist","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1101\/gr.8.9.871","article-title":"The synuclein family","volume":"8","author":"Lavedan","year":"1998","journal-title":"Genome Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1523\/JNEUROSCI.08-08-02804.1988","article-title":"Synuclein: A neuron-specific protein localized to the nucleus and presynaptic nerve terminal","volume":"8","author":"Maroteaux","year":"1988","journal-title":"J. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.neuron.2013.09.004","article-title":"The function of \u03b1-synuclein","volume":"79","author":"Bendor","year":"2013","journal-title":"Neuron"},{"key":"ref_52","unstructured":"George, J.M. (2002). The synucleins. Genome Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nature10324","article-title":"\u03b1-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation","volume":"477","author":"Bartels","year":"2011","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"17797","DOI":"10.1073\/pnas.1113260108","article-title":"A soluble alpha-synuclein construct forms a dynamic tetramer","volume":"108","author":"Wang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/j.1749-6632.2000.tb06903.x","article-title":"Accelerated oligomerization by Parkinson\u2019s disease linked \u03b1-synuclein mutants","volume":"920","author":"Conway","year":"2000","journal-title":"Ann. NY Acad. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1126\/science.1063522","article-title":"Kinetic stabilization of the \u03b1-synuclein protofibril by a dopamine\u2014\u03b1-Synuclein adduct","volume":"294","author":"Conway","year":"2001","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/ncb748","article-title":"\u03b1-Synuclein is phosphorylated in synucleinopathy lesions","volume":"4","author":"Fujiwara","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1111\/j.1742-4658.2011.08093.x","article-title":"Modulation of \u03b1-synuclein aggregation by dopamine in the presence of MPTP and its metabolite","volume":"278","author":"Jethva","year":"2011","journal-title":"FEBS J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4901","DOI":"10.1021\/bi972776r","article-title":"Regulation of phospholipase D2: Selective inhibition of mammalian phospholipase D isoenzymes by alpha- and beta-synucleins","volume":"37","author":"Jenco","year":"1998","journal-title":"Biochemistry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3214","DOI":"10.1523\/JNEUROSCI.20-09-03214.2000","article-title":"Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons","volume":"20","author":"Murphy","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8797","DOI":"10.1523\/JNEUROSCI.22-20-08797.2002","article-title":"Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein","volume":"22","author":"Cabin","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"14966","DOI":"10.1073\/pnas.0406283101","article-title":"Double-knockout mice for alpha- and beta-synucleins: Effect on synaptic functions","volume":"101","author":"Chandra","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7438","DOI":"10.1074\/jbc.M112.439497","article-title":"\u03b1-Synuclein membrane association is regulated by the Rab3a recycling machinery and presynaptic activity","volume":"288","author":"Chen","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1523\/JNEUROSCI.4308-05.2006","article-title":"Parkinson\u2019s disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death","volume":"26","author":"Martin","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"9089","DOI":"10.1074\/jbc.M710012200","article-title":"Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain","volume":"283","author":"Devi","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.neulet.2009.02.056","article-title":"alpha-Synuclein is differentially expressed in mitochondria from different rat brain regions and dose-dependently down-regulates complex I activity","volume":"454","author":"Liu","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.neulet.2010.09.061","article-title":"Mitochondrial \u03b1-synuclein accumulation impairs complex I function in dopaminergic neurons and results in increased mitophagy in vivo","volume":"486","author":"Chinta","year":"2010","journal-title":"Neurosci. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"20710","DOI":"10.1074\/jbc.M110.213538","article-title":"Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein alpha-synuclein","volume":"286","author":"Nakamura","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1126\/science.1129462","article-title":"Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson\u2019s models","volume":"313","author":"Cooper","year":"2006","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1073\/pnas.0710685105","article-title":"The Parkinson\u2019s disease protein alpha-synuclein disrupts cellular Rab homeostasis","volume":"105","author":"Gitler","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1091\/mbc.e09-09-0801","article-title":"Alpha-synuclein delays endoplasmic reticulum (ER)-to-Golgi transport in mammalian cells by antagonizing ER\/Golgi SNAREs","volume":"21","author":"Thayanidhi","year":"2010","journal-title":"Mol. Biol. Cell."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"14508","DOI":"10.1523\/JNEUROSCI.1560-11.2011","article-title":"Distinct roles in vivo for the ubiquitin-proteasome system and the autophagy-lysosomal pathway in the degradation of \u03b1-synuclein","volume":"31","author":"Fan","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"7812","DOI":"10.1021\/bi0102398","article-title":"Vesicle permeabilization by protofibrillar alpha-synuclein: Implications for the pathogenesis and treatment of Parkinson\u2019s disease","volume":"40","author":"Volles","year":"2001","journal-title":"Biochemistry"},{"key":"ref_74","first-page":"461","article-title":"The role of oxidative stress in Parkinson\u2019s disease","volume":"3","author":"Dias","year":"2013","journal-title":"J. Park. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"324","DOI":"10.5607\/en.2014.23.4.324","article-title":"Protein transmission, seeding and degradation: key steps for \u03b1-synuclein prion-like propagation","volume":"23","author":"Oueslati","year":"2014","journal-title":"Exp. Neurobiol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Surgucheva, I., Newell, K.L., Burns, J., and Surguchov, A. (2014). New \u03b1- and \u03b3-synuclein immunopathological lesions in human brain. Acta Neuropathol Commun.","DOI":"10.1186\/s40478-014-0132-8"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"29739","DOI":"10.1074\/jbc.M600933200","article-title":"Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease","volume":"281","author":"Anderson","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6365","DOI":"10.1523\/JNEUROSCI.20-17-06365.2000","article-title":"Subcellular localization of wild-type and Parkinson\u2019s disease-associated mutant alpha-synuclein in human and transgenic mouse brain","volume":"20","author":"Kahle","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"42225","DOI":"10.1074\/jbc.M213217200","article-title":"Identification and characterization of a novel Pyk2\/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein phosphorylation","volume":"278","author":"Takahashi","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_80","first-page":"872","article-title":"Phosphorylation does not prompt, nor prevent, the formation of \u03b1-synuclein toxic species in a rat model of Parkinson\u2019s disease","volume":"18","author":"Schneider","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1097\/NEN.0b013e3181a24b53","article-title":"Alpha-synuclein S129 phosphorylation mutants do not alter nigrostriatal toxicity in a rat model of Parkinson disease","volume":"68","author":"McFarland","year":"2009","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1515\/revneuro-2012-0071","article-title":"The role of Ser129 phosphorylation of \u03b1-synuclein in neurodegeneration of Parkinson\u2019s disease: Areview of in vivo models","volume":"24","author":"Sato","year":"2013","journal-title":"Rev. Neurosci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1097\/NEN.0b013e3186fc995","article-title":"Specificity and regulation of casein kinase-mediated phosphorylation of alpha-synuclein","volume":"67","author":"Waxman","year":"2008","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1074\/jbc.M109.081950","article-title":"Phosphorylation of synucleins by members of the Polo-like kinase family","volume":"285","author":"Mbefo","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"7604","DOI":"10.1523\/JNEUROSCI.0297-11.2011","article-title":"Induction of intracellular tau aggregation is promoted by \u03b1-synuclein seeds and provides novel insights into the hyperphosphorylation of tau","volume":"31","author":"Waxman","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Tenreiro, S., Eckermann, K., and Outeiro, T.F. (2014). Protein phosphorylation in neurodegeneration: Friend or foe?. Front. Mol. Neurosci.","DOI":"10.3389\/fnmol.2014.00042"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"E3945","DOI":"10.1073\/pnas.1309991110","article-title":"Polo-like kinase 2 regulates selective autophagic \u03b1-synuclein clearance and suppresses its toxicity in vivo","volume":"110","author":"Oueslati","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"630","DOI":"10.2174\/18715273113126660195","article-title":"\u03b1-Synuclein ubiquitination and novel therapeutic targets for Parkinson\u2019s disease","volume":"13","author":"Rott","year":"2014","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"17726","DOI":"10.1073\/pnas.1315654110","article-title":"Synthetic polyubiquitinated \u03b1-synuclein reveals important insights into the roles of the ubiquitin chain in regulating its pathophysiology","volume":"110","author":"Fauvet","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3942","DOI":"10.1523\/JNEUROSCI.4965-05.2006","article-title":"Pathological changes in dopaminergic nerve cells of the substantia nigra and olfactory bulb in mice transgenic for truncated human \u03b1-synuclein (1\u2013120): Implications for Lewy body disorders","volume":"26","author":"Tofaris","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"18344","DOI":"10.1074\/jbc.M000206200","article-title":"Dityrosine cross-linking promotes formation of stable alpha-synuclein polymers. Implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies","volume":"275","author":"Souza","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1046\/j.1471-4159.2000.740721.x","article-title":"\u03b1-Synuclein up-regulation in substantia nigra dopaminergic neurons following administration of the parkinsonian toxin MPTP","volume":"74","author":"Vila","year":"2000","journal-title":"J. Neurochem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S0002-9440(10)64553-1","article-title":"Alpha-synuclein promotes mitochondrial deficit and oxidative stress","volume":"157","author":"Hsu","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"28849","DOI":"10.1074\/jbc.274.41.28849","article-title":"Role of cytochrome C as a stimulator of alpha-synuclein aggregation in Lewy body disease","volume":"274","author":"Hashimoto","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_95","first-page":"205","article-title":"Generation of ferric iron links oxidative stress to \u03b1-synuclein oligomer formation","volume":"1","author":"Levin","year":"2011","journal-title":"J. Park. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/S0891-5849(02)00741-4","article-title":"Aggregation of \u03b1-synuclein induced by the Cu, Zn-superoxide dismutase and hydrogen peroxide system","volume":"32","author":"Kim","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"8465","DOI":"10.1021\/bi0341152","article-title":"Nuclear localization of alpha-synuclein and its interaction with histones","volume":"42","author":"Goers","year":"2003","journal-title":"Biochemistry"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.bbrc.2006.01.148","article-title":"Oxidative stress induces nuclear translocation of C-terminus of alpha-synuclein in dopaminergic cells","volume":"342","author":"Xu","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.brainres.2013.01.024","article-title":"Nuclear translocation of alpha-synuclein increases susceptibility of MES23.5 cells to oxidative stress","volume":"1500","author":"Zhou","year":"2013","journal-title":"Brain Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1016\/j.febslet.2006.03.018","article-title":"Alpha-synuclein facilitates the toxicity of oxidized catechol metabolites: Implications for selective neurodegeneration in Parkinson\u2019s disease","volume":"580","author":"Hasegawa","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1385\/MN:31:1-3:243","article-title":"\u03b1-Synuclein and dopamine metabolism","volume":"31","author":"Yu","year":"2005","journal-title":"Mol. Neurobiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/S0306-4522(03)00036-8","article-title":"Role of alpha-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice","volume":"118","author":"Fornai","year":"2003","journal-title":"Neuroscience"},{"key":"ref_103","first-page":"324","article-title":"Dual effects of different concentrations of alpha-synuclein on the neurotoxicity of 6-hydroxydopamine in SH-SY5Y cells","volume":"61","author":"Zhou","year":"2009","journal-title":"Sheng Li Xue Bao"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e16706","DOI":"10.1371\/journal.pone.0016706","article-title":"Resistance to MPTP-neurotoxicity in \u03b1-synuclein knockout mice is complemented by human \u03b1-synuclein and associated with increased \u03b2-synuclein and Akt activation","volume":"6","author":"Thomas","year":"2011","journal-title":"PLoS ONE"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.nbd.2005.08.018","article-title":"Mice lacking alpha-synuclein are resistant to mitochondrial toxins","volume":"21","author":"Klivenyi","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1097\/00005072-196507000-00003","article-title":"Phase and electron microscopic observations of Lewy bodies and melanin granules in the substantia nigra and locus coeruleus in Parkinson\u2019s disease","volume":"24","author":"Duffy","year":"1965","journal-title":"J. Neuropthol. Exp. Neurol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1212\/wnl.18.8.817","article-title":"Studies on neuromelanin. II. Melanin in the brainstems of infants and children","volume":"18","author":"Fenichel","year":"1968","journal-title":"Neurology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/j.1600-0749.1994.tb00061.x","article-title":"X-ray characterization of melanins\u2013II","volume":"7","author":"Cheng","year":"1994","journal-title":"Pigment Cell Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1046\/j.1471-4159.1997.69041720.x","article-title":"L-DOPA is a substrate for tyrosine hydroxylase","volume":"69","author":"Haavik","year":"1997","journal-title":"J. Neurochem."},{"key":"ref_110","first-page":"15","article-title":"The role of peroxidase in neuromelanin synthesis: A review","volume":"29","author":"Okun","year":"1997","journal-title":"Physiol. Chem. Phys. Med. NMR"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"11869","DOI":"10.1073\/pnas.97.22.11869","article-title":"Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles","volume":"97","author":"Sulzer","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1126\/science.3080808","article-title":"Selectivity of the parkinsonian neurotoxin MPTP: Toxic metabolite MPP+ binds to neuromelanin","volume":"231","author":"Lipman","year":"1986","journal-title":"Science"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1600-0749.1987.tb00403.x","article-title":"Neuromelanin and its possible protective and destructive properties","volume":"1","author":"Lindquist","year":"1987","journal-title":"Pigment Cell Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1046\/j.1471-4159.1994.62031097.x","article-title":"Iron and other metals in neuromelanin, substantia nigra, and putamen of human brain","volume":"62","author":"Zecca","year":"1994","journal-title":"J. Neurochem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/BF02263482","article-title":"The apparent autoxidation rate of catechols in dopamine-rich regions of human brains increases with the degree of depigmentation of substantia nigra","volume":"1","author":"Fornstedt","year":"1989","journal-title":"J. Neural Transm. Park. Dis. Dement Sect."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/BF03033277","article-title":"Model neuromelanins as antioxidative agents during lipid peroxidation","volume":"1","author":"Wilczok","year":"1999","journal-title":"Neurotox. Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1007\/s00702-004-0211-2","article-title":"Neuromelanin inhibits enzymatic activity of 26S proteasome in human dopaminergic SH-SY5Y cells","volume":"111","author":"Maruyama","year":"2004","journal-title":"J. Neural Transm."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0925-4439(95)00058-C","article-title":"The effect of a synthetic neruomelanin on yield of free hydroxyl radicals generated in model systems","volume":"1271","author":"Zareba","year":"1995","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1046\/j.1471-4159.2003.01917.x","article-title":"The structure of neuromelanin as studied by chemical degradative methods","volume":"86","author":"Wakamatsu","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/j.1600-0749.1998.tb00721.x","article-title":"Chemical degradation of melanins: Application to identification of dopamine-melanin","volume":"11","author":"Ito","year":"1998","journal-title":"Pigment Cell Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1093\/brain\/awh584","article-title":"Alpha-synuclein redistributes to neuromelanin lipid in the substantia nigra early in Parkinson\u2019s disease","volume":"128","author":"Halliday","year":"2005","journal-title":"Brain"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1007\/s12035-013-8586-4","article-title":"Role and mechanism of microglial activation in iron-induced selective and progressive dopaminergic neurodegeneration","volume":"49","author":"Zhang","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1096\/fj.02-0314fje","article-title":"Activation of microglia by human neuromelanin is NF-kappaB dependent and involves p38 mitogen-activated protein kinase: Implications for Parkinson\u2019s disease","volume":"17","author":"Wilms","year":"2003","journal-title":"FASEB J."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s12640-013-9435-y","article-title":"Neuromelanin of the human substantia nigra: An update","volume":"25","author":"Zucca","year":"2014","journal-title":"Neurotox. Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s00702-003-0080-0","article-title":"Longterm retention of neurotoxic beta-carbolines in brain neuromelanin","volume":"111","author":"Ostergren","year":"2004","journal-title":"J. Neural Transm."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0304-3940(88)90002-X","article-title":"Autoradiography of [14C]paraquat or [14C]diquat in frogs and mice: Accumulation in neuromelanin","volume":"93","author":"Lindquist","year":"1988","journal-title":"Neurosci. Lett."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1111\/j.1600-0749.2004.00201.x","article-title":"The neuromelanin of human substantia nigra: Physiological and pathogenic aspects","volume":"17","author":"Zucca","year":"2004","journal-title":"Pigment Cell Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/0925-4439(92)90144-C","article-title":"The chemical characterization of melanin contained in substantia nigra of human brain","volume":"1138","author":"Zecca","year":"1992","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1046\/j.1471-4159.2000.0741758.x","article-title":"Interaction of human substantia nigra neuromelanin with lipids and peptides","volume":"74","author":"Zecca","year":"2000","journal-title":"J. Neurochem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1046\/j.1471-4159.1994.62010369.x","article-title":"Evidence for a glycidic-lipidic matrix in human neuromelanin, potentially responsible for the enhanced iron sequestering ability of substantia nigra","volume":"62","author":"Aime","year":"1994","journal-title":"J. Neurochem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1097\/00005072-196907000-00005","article-title":"The histochemical relationship of neuromelanin and lipofuscin","volume":"28","author":"Barden","year":"1969","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"S69","DOI":"10.1002\/ana.410320712","article-title":"Modulation by neuromelanin of the availability and reactivity of metal ions","volume":"32","author":"Swartz","year":"1992","journal-title":"Ann. Neurol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s00702-006-0453-2","article-title":"Neuromelanin and iron in human locus coeruleus and substantia nigra during aging: Consequences for neuronal vulnerability","volume":"113","author":"Zucca","year":"2006","journal-title":"J. Neural. Transm."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1046\/j.1471-4159.2003.01923.x","article-title":"Neuromelanin associated redox-active iron is increased in the substantia nigra of patients with Parkinson\u2019s disease","volume":"86","author":"Faucheux","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S0006-2952(03)00293-4","article-title":"Iron-binding characteristics of neuromelanin of the human substantia nigra","volume":"66","author":"Double","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1111\/j.1471-4159.1991.tb06358.x","article-title":"Iron-melanin interaction and lipid peroxidation: Implications for Parkinson\u2019s disease","volume":"57","author":"Riederer","year":"1991","journal-title":"J. Neurochem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/978-1-61779-163-5_30","article-title":"UV-laser microdissection and mRNA expression analysis of individual neurons from postmortem Parkinson\u2019s disease brains","volume":"755","author":"Schlaudraff","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"e10481","DOI":"10.1371\/journal.pone.0010481","article-title":"Parkinson\u2019s disease-related protein, \u03b1-synuclein, in malignant melanoma","volume":"5","author":"Matsuo","year":"2010","journal-title":"PLoS ONE"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0197-0186(02)00161-4","article-title":"Residual substantia nigra neuromelanin in Parkinson\u2019s disease is cross-linked to alpha-synuclein","volume":"42","author":"Fasano","year":"2003","journal-title":"Neurochem. Int."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.neurobiolaging.2005.02.015","article-title":"Evidence for specific phases in the development of human neuromelanin","volume":"27","author":"Fedorow","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.nbd.2006.08.021","article-title":"Age-associated increases of alpha-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: Is this the target for Parkinson\u2019s disease?","volume":"25","author":"Chu","year":"2007","journal-title":"Neurobiol. Dis."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/S0892-0362(02)00218-0","article-title":"Influence of neuromelanin on oxidative pathways within the human substantia nigra","volume":"24","author":"Double","year":"2002","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s00702-005-0410-5","article-title":"Neuromelanin induces oxidative stress in mitochondria through release of iron: Mechanism behind the inhibition of 26S proteasome","volume":"113","author":"Maruyama","year":"2006","journal-title":"J. Neural Transm."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.tins.2007.03.009","article-title":"Multiple hit hypotheses for dopamine neuron loss in Parkinson's disease","volume":"30","author":"Sulzer","year":"2007","journal-title":"Trends Neurosci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"25009","DOI":"10.1074\/jbc.M300227200","article-title":"Alpha-Synuclein is degraded by both autophagy and the proteasome","volume":"278","author":"Webb","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"e45183","DOI":"10.1371\/journal.pone.0045183","article-title":"The role of alpha-synuclein in melanin synthesis in melanoma and dopaminergic neuronal cells","volume":"7","author":"Pan","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-3-7091-0643-3_8","article-title":"The neuromelanin of human substantia nigra: Structure, synthesis and molecular behaviour","volume":"65","author":"Zecca","year":"2003","journal-title":"J. Neural Transm. Suppl."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1111\/pcmr.12014","article-title":"Biosynthetic pathway to neuromelanin and its aging process","volume":"25","author":"Wakamatsu","year":"2012","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"16808","DOI":"10.1074\/jbc.M709014200","article-title":"The reaction of alpha-synuclein with tyrosinase: Possible implications for Parkinson disease","volume":"283","author":"Tessari","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_150","first-page":"130","article-title":"\u03b1-Synuclein functions as a negative regulator for expression of tyrosine hudroxylase","volume":"111","author":"Li","year":"2011","journal-title":"Acta Neurol. Belg."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/j.bbapap.2013.03.008","article-title":"\u03b1-Synuclein-mediated defense against oxidative stress via modulation of glutathione peroxidase","volume":"1834","author":"Koo","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/0028-3908(86)90242-X","article-title":"Occurrence and distribution of 5-S-cysteinyl derivatives of dopamine, dopa and dopac in the brains of eight mammalian species","volume":"25","author":"Fornstedt","year":"1986","journal-title":"Neuropharmacology"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/cne.20098","article-title":"Inverse relationship between the contents of neuromelanin pigment and the vesicular monoamine transporter-2: Human midbrain dopamine neurons","volume":"473","author":"Liang","year":"2004","journal-title":"J. Comp. Neurol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.neulet.2004.05.118","article-title":"Inhibition of tyrosine hydroxylase expression in alpha-synuclein-transfected dopaminergic neuronal cells","volume":"367","author":"Yu","year":"2004","journal-title":"Neurosci. Lett."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0896-6273(00)80886-7","article-title":"Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system","volume":"25","author":"Abeliovich","year":"2000","journal-title":"Neuron"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"11915","DOI":"10.1523\/JNEUROSCI.3821-06.2006","article-title":"Alpha-synuclein overexpression in PC12 and chromaffin cells impairs catecholamine release by interfering with a late step in exocytosis","volume":"26","author":"Larsen","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"e27959","DOI":"10.1371\/journal.pone.0027959","article-title":"Redistribution of DAT\/\u03b1-synuclein complexes visualized by \u201cin situ\u201d proximity ligation assay in transgenic mice modelling early Parkinson\u2019s disease","volume":"6","author":"Bellucci","year":"2011","journal-title":"PLoS ONE"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"e70872","DOI":"10.1371\/journal.pone.0070872","article-title":"Synucleins antagonize endoplasmic reticulum function to modulate dopamine transporter trafficking","volume":"8","author":"Oaks","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/nrn983","article-title":"Pathogenesis of Parkinson\u2019s disease: Dopamine, vesicles and \u03b1-synuclein","volume":"3","author":"Lotharius","year":"2002","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"38884","DOI":"10.1074\/jbc.M205518200","article-title":"Effect of mutant \u03b1-synuclein on dopamine homeostasis in a new human mesencephalic cell line","volume":"277","author":"Lotharius","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"9304","DOI":"10.1523\/JNEUROSCI.0519-06.2006","article-title":"Alpha-synuclein overexpression increases cytosolic catecholamine concentration","volume":"26","author":"Mosharov","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1021\/cn300034t","article-title":"Oxidative stress effect of dopamine on \u03b1-synuclein: Electroanalysis of solvent interactions","volume":"3","author":"Chan","year":"2012","journal-title":"ACS Chem. Neurosci."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/5\/2\/1122\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:47:32Z","timestamp":1760215652000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/5\/2\/1122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,5]]},"references-count":162,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2015,6]]}},"alternative-id":["biom5021122"],"URL":"https:\/\/doi.org\/10.3390\/biom5021122","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,5]]}}}