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Neuromelanin in Parkinson’s Disease: Tyrosine Hydroxylase and Tyrosinase
Parkinson’s disease (PD) is an aging-related disease and the second most common neurodegenerative disease after Alzheimer’s disease. The main symptoms of PD are movement disorders accompanied with deficiency of neurotransmitter dopamine (DA) in the striatum due to cell death of the nigrostriatal DA...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029562/ https://www.ncbi.nlm.nih.gov/pubmed/35456994 http://dx.doi.org/10.3390/ijms23084176 |
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author | Nagatsu, Toshiharu Nakashima, Akira Watanabe, Hirohisa Ito, Shosuke Wakamatsu, Kazumasa |
author_facet | Nagatsu, Toshiharu Nakashima, Akira Watanabe, Hirohisa Ito, Shosuke Wakamatsu, Kazumasa |
author_sort | Nagatsu, Toshiharu |
collection | PubMed |
description | Parkinson’s disease (PD) is an aging-related disease and the second most common neurodegenerative disease after Alzheimer’s disease. The main symptoms of PD are movement disorders accompanied with deficiency of neurotransmitter dopamine (DA) in the striatum due to cell death of the nigrostriatal DA neurons. Two main histopathological hallmarks exist in PD: cytosolic inclusion bodies termed Lewy bodies that mainly consist of α-synuclein protein, the oligomers of which produced by misfolding are regarded to be neurotoxic, causing DA cell death; and black pigments termed neuromelanin (NM) that are contained in DA neurons and markedly decrease in PD. The synthesis of human NM is regarded to be similar to that of melanin in melanocytes; melanin synthesis in skin is via DOPAquinone (DQ) by tyrosinase, whereas NM synthesis in DA neurons is via DAquinone (DAQ) by tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). DA in cytoplasm is highly reactive and is assumed to be oxidized spontaneously or by an unidentified tyrosinase to DAQ and then, synthesized to NM. Intracellular NM accumulation above a specific threshold has been reported to be associated with DA neuron death and PD phenotypes. This review reports recent progress in the biosynthesis and pathophysiology of NM in PD. |
format | Online Article Text |
id | pubmed-9029562 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90295622022-04-23 Neuromelanin in Parkinson’s Disease: Tyrosine Hydroxylase and Tyrosinase Nagatsu, Toshiharu Nakashima, Akira Watanabe, Hirohisa Ito, Shosuke Wakamatsu, Kazumasa Int J Mol Sci Review Parkinson’s disease (PD) is an aging-related disease and the second most common neurodegenerative disease after Alzheimer’s disease. The main symptoms of PD are movement disorders accompanied with deficiency of neurotransmitter dopamine (DA) in the striatum due to cell death of the nigrostriatal DA neurons. Two main histopathological hallmarks exist in PD: cytosolic inclusion bodies termed Lewy bodies that mainly consist of α-synuclein protein, the oligomers of which produced by misfolding are regarded to be neurotoxic, causing DA cell death; and black pigments termed neuromelanin (NM) that are contained in DA neurons and markedly decrease in PD. The synthesis of human NM is regarded to be similar to that of melanin in melanocytes; melanin synthesis in skin is via DOPAquinone (DQ) by tyrosinase, whereas NM synthesis in DA neurons is via DAquinone (DAQ) by tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). DA in cytoplasm is highly reactive and is assumed to be oxidized spontaneously or by an unidentified tyrosinase to DAQ and then, synthesized to NM. Intracellular NM accumulation above a specific threshold has been reported to be associated with DA neuron death and PD phenotypes. This review reports recent progress in the biosynthesis and pathophysiology of NM in PD. MDPI 2022-04-10 /pmc/articles/PMC9029562/ /pubmed/35456994 http://dx.doi.org/10.3390/ijms23084176 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Nagatsu, Toshiharu Nakashima, Akira Watanabe, Hirohisa Ito, Shosuke Wakamatsu, Kazumasa Neuromelanin in Parkinson’s Disease: Tyrosine Hydroxylase and Tyrosinase |
title | Neuromelanin in Parkinson’s Disease: Tyrosine Hydroxylase and Tyrosinase |
title_full | Neuromelanin in Parkinson’s Disease: Tyrosine Hydroxylase and Tyrosinase |
title_fullStr | Neuromelanin in Parkinson’s Disease: Tyrosine Hydroxylase and Tyrosinase |
title_full_unstemmed | Neuromelanin in Parkinson’s Disease: Tyrosine Hydroxylase and Tyrosinase |
title_short | Neuromelanin in Parkinson’s Disease: Tyrosine Hydroxylase and Tyrosinase |
title_sort | neuromelanin in parkinson’s disease: tyrosine hydroxylase and tyrosinase |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029562/ https://www.ncbi.nlm.nih.gov/pubmed/35456994 http://dx.doi.org/10.3390/ijms23084176 |
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