Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson's disease pathogenesis
Brain tyrosinase; Neuromelanin production; Parkinson’s
| Authors: | , , , , , , , , , , , |
|---|---|
| Format: | article |
| Status: | Published version |
| Publication Date: | 2019 |
| Country: | España |
| Institution: | Departament de Salut de la Generalitat de Catalunya (DS) |
| Repository: | Scientia. Dipòsit d'Informació Digital del Departament de Salut |
| OAI Identifier: | oai:scientiasalut.gencat.cat:11351/3883 |
| Online Access: | https://hdl.handle.net/11351/3883 |
| Access Level: | Open access |
| Keyword: | Parkinson, Malaltia de Aminoàcids - Metabolisme DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian Disorders::Parkinson Disease CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Amino Acids, Aromatic::Tyrosine::Melanins CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Amino Acids, Aromatic::Tyrosine Other subheadings::Other subheadings::Other subheadings::/metabolism ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades de los ganglios basales::trastornos parkinsonianos::enfermedad de Parkinson COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::aminoácidos::aminoácidos cíclicos::aminoácidos aromáticos::tirosina::melaninas COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::aminoácidos::aminoácidos cíclicos::aminoácidos aromáticos::tirosina Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo |
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Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson's disease pathogenesisCarballo Carbajal, IriaRomero Gimenez, JordiCuadros Arasa, ThaisBove Badell, JordiMartínez Vicente, MartaPeñuelas Peñarroya, NúriaTorra i Talavera, AlbertRodríguez Galván, BeatrizVila Bover, MiquelGonzález Sepúlveda, MartaLaguna Tuset, AriadnaParent, AnnabelleParkinson, Malaltia deAminoàcids - MetabolismeDISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian Disorders::Parkinson DiseaseCHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Amino Acids, Aromatic::Tyrosine::MelaninsCHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Amino Acids, Aromatic::TyrosineOther subheadings::Other subheadings::Other subheadings::/metabolismENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades de los ganglios basales::trastornos parkinsonianos::enfermedad de ParkinsonCOMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::aminoácidos::aminoácidos cíclicos::aminoácidos aromáticos::tirosina::melaninasCOMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::aminoácidos::aminoácidos cíclicos::aminoácidos aromáticos::tirosinaOtros calificadores::Otros calificadores::Otros calificadores::/metabolismoBrain tyrosinase; Neuromelanin production; Parkinson’sTirosinasa cerebral; Producció de neuromelanina; ParkinsonTirosinasa cerebral; Producción de neuromelanina; ParkinsonIn Parkinson's disease (PD) there is a selective degeneration of neuromelanin-containing neurons, especially substantia nigra dopaminergic neurons. In humans, neuromelanin accumulates with age, the latter being the main risk factor for PD. The contribution of neuromelanin to PD pathogenesis remains unknown because, unlike humans, common laboratory animals lack neuromelanin. Synthesis of peripheral melanins is mediated by tyrosinase, an enzyme also present at low levels in the brain. Here we report that overexpression of human tyrosinase in rat substantia nigra results in age-dependent production of human-like neuromelanin within nigral dopaminergic neurons, up to levels reached in elderly humans. In these animals, intracellular neuromelanin accumulation above a specific threshold is associated to an age-dependent PD phenotype, including hypokinesia, Lewy body-like formation and nigrostriatal neurodegeneration. Enhancing lysosomal proteostasis reduces intracellular neuromelanin and prevents neurodegeneration in tyrosinase-overexpressing animals. Our results suggest that intracellular neuromelanin levels may set the threshold for the initiation of PD.Nature ResearchInstitut Català de la Salut[Carballo-Carbajal I, Laguna A, Romero-Giménez J, Cuadros T, Bové J, Martinez-Vicente M, Parent A, Gonzalez-Sepulveda M, Peñuelas N, Torra A, Rodríguez-Galván B] Grup de recerca en Malalties Neurodegeneratives, Vall d’Hebron Institut de Recerca, Barcelona, Spain. [Vila M] Grup de recerca en Malalties Neurodegeneratives, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, Barcelona, Spain. Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.Vall d'Hebron Barcelona Hospital Campus201920192019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/3883Scientiareponame:Scientia. Dipòsit d'Informació Digital del Departament de Salutinstname:Departament de Salut de la Generalitat de Catalunya (DS)InglésNature Communications;(10)1https://www.nature.com/articles/s41467-019-08858-yAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:scientiasalut.gencat.cat:11351/38832026-06-12T09:38:37Z |
| dc.title.none.fl_str_mv |
Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson's disease pathogenesis |
| title |
Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson's disease pathogenesis |
| spellingShingle |
Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson's disease pathogenesis Carballo Carbajal, Iria Parkinson, Malaltia de Aminoàcids - Metabolisme DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian Disorders::Parkinson Disease CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Amino Acids, Aromatic::Tyrosine::Melanins CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Amino Acids, Aromatic::Tyrosine Other subheadings::Other subheadings::Other subheadings::/metabolism ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades de los ganglios basales::trastornos parkinsonianos::enfermedad de Parkinson COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::aminoácidos::aminoácidos cíclicos::aminoácidos aromáticos::tirosina::melaninas COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::aminoácidos::aminoácidos cíclicos::aminoácidos aromáticos::tirosina Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo |
| title_short |
Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson's disease pathogenesis |
| title_full |
Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson's disease pathogenesis |
| title_fullStr |
Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson's disease pathogenesis |
| title_full_unstemmed |
Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson's disease pathogenesis |
| title_sort |
Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson's disease pathogenesis |
| dc.creator.none.fl_str_mv |
Carballo Carbajal, Iria Romero Gimenez, Jordi Cuadros Arasa, Thais Bove Badell, Jordi Martínez Vicente, Marta Peñuelas Peñarroya, Núria Torra i Talavera, Albert Rodríguez Galván, Beatriz Vila Bover, Miquel González Sepúlveda, Marta Laguna Tuset, Ariadna Parent, Annabelle |
| author |
Carballo Carbajal, Iria |
| author_facet |
Carballo Carbajal, Iria Romero Gimenez, Jordi Cuadros Arasa, Thais Bove Badell, Jordi Martínez Vicente, Marta Peñuelas Peñarroya, Núria Torra i Talavera, Albert Rodríguez Galván, Beatriz Vila Bover, Miquel González Sepúlveda, Marta Laguna Tuset, Ariadna Parent, Annabelle |
| author_role |
author |
| author2 |
Romero Gimenez, Jordi Cuadros Arasa, Thais Bove Badell, Jordi Martínez Vicente, Marta Peñuelas Peñarroya, Núria Torra i Talavera, Albert Rodríguez Galván, Beatriz Vila Bover, Miquel González Sepúlveda, Marta Laguna Tuset, Ariadna Parent, Annabelle |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Institut Català de la Salut [Carballo-Carbajal I, Laguna A, Romero-Giménez J, Cuadros T, Bové J, Martinez-Vicente M, Parent A, Gonzalez-Sepulveda M, Peñuelas N, Torra A, Rodríguez-Galván B] Grup de recerca en Malalties Neurodegeneratives, Vall d’Hebron Institut de Recerca, Barcelona, Spain. [Vila M] Grup de recerca en Malalties Neurodegeneratives, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, Barcelona, Spain. Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain. Vall d'Hebron Barcelona Hospital Campus |
| dc.subject.none.fl_str_mv |
Parkinson, Malaltia de Aminoàcids - Metabolisme DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian Disorders::Parkinson Disease CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Amino Acids, Aromatic::Tyrosine::Melanins CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Amino Acids, Aromatic::Tyrosine Other subheadings::Other subheadings::Other subheadings::/metabolism ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades de los ganglios basales::trastornos parkinsonianos::enfermedad de Parkinson COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::aminoácidos::aminoácidos cíclicos::aminoácidos aromáticos::tirosina::melaninas COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::aminoácidos::aminoácidos cíclicos::aminoácidos aromáticos::tirosina Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo |
| topic |
Parkinson, Malaltia de Aminoàcids - Metabolisme DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian Disorders::Parkinson Disease CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Amino Acids, Aromatic::Tyrosine::Melanins CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Amino Acids, Aromatic::Tyrosine Other subheadings::Other subheadings::Other subheadings::/metabolism ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades de los ganglios basales::trastornos parkinsonianos::enfermedad de Parkinson COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::aminoácidos::aminoácidos cíclicos::aminoácidos aromáticos::tirosina::melaninas COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::aminoácidos::aminoácidos cíclicos::aminoácidos aromáticos::tirosina Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo |
| description |
Brain tyrosinase; Neuromelanin production; Parkinson’s |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2019 2019 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/11351/3883 |
| url |
https://hdl.handle.net/11351/3883 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Nature Communications;(10)1 https://www.nature.com/articles/s41467-019-08858-y |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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application/pdf |
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Nature Research |
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Nature Research |
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Scientia reponame:Scientia. Dipòsit d'Informació Digital del Departament de Salut instname:Departament de Salut de la Generalitat de Catalunya (DS) |
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Departament de Salut de la Generalitat de Catalunya (DS) |
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Scientia. Dipòsit d'Informació Digital del Departament de Salut |
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Scientia. Dipòsit d'Informació Digital del Departament de Salut |
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1869420580247175168 |
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15.811543 |