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The role of tyrosine hydroxylase as a key player in neuromelanin synthesis and the association of neuromelanin with Parkinson’s disease

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Název: The role of tyrosine hydroxylase as a key player in neuromelanin synthesis and the association of neuromelanin with Parkinson’s disease
Autoři: Toshiharu Nagatsu, Akira Nakashima, Hirohisa Watanabe, Shosuke Ito, Kazumasa Wakamatsu, Fabio A. Zucca, Luigi Zecca, Moussa Youdim, Maximilian Wulf, Peter Riederer, Johannes M. Dijkstra
Zdroj: J Neural Transm (Vienna)
Journal of neural transmission 130 (2023): 611–625. doi:10.1007/s00702-023-02617-6
info:cnr-pdr/source/autori:Nagatsu T.; Nakashima A.; Watanabe H.; Ito S.; Wakamatsu K.; Zucca F.A.; Zecca L.; Youdim M.; Wulf M.; Riederer P.; Dijkstra J.M./titolo:The role of tyrosine hydroxylase as a key player in neuromelanin synthesis and the association of neuromelanin with Parkinson's disease/doi:10.1007%2Fs00702-023-02617-6/rivista:Journal of neural transmission/anno:2023/pagina_da:611/pagina_a:625/intervallo_pagine:611–625/volume:130
Informace o vydavateli: Springer Science and Business Media LLC, 2023.
Rok vydání: 2023
Témata: Tyrosine 3-Monooxygenase/metabolism, Tyrosine 3-Monooxygenase, Dopamine, Parkinson's disease, Norepinephrine/metabolism, tyrosinase, Neuromelanin, norepinephrine, Dopaminergic Neurons/metabolism, Neurology and Preclinical Neurological Studies - Review Article, Norepinephrine, Catecholamines, Cysteine/metabolism, tyrosine hydroxylase, Melanin, Locus coeruleus, Substantia nigra, Humans, Cysteine, Substantia Nigra/metabolism, Melanins, Catecholamines/metabolism, Melanins/metabolism, locus coeruleus, Dopaminergic Neurons, Parkinson Disease, Parkinson Disease/metabolism, melanin, Substantia Nigra, substantia nigra, Tyrosinase, Tyrosine hydroxylase, dopamine, neuromelanin
Popis: The dark pigment neuromelanin (NM) is abundant in cell bodies of dopamine (DA) neurons in the substantia nigra (SN) and norepinephrine (NE) neurons in the locus coeruleus (LC) in the human brain. During the progression of Parkinson’s disease (PD), together with the degeneration of the respective catecholamine (CA) neurons, the NM levels in the SN and LC markedly decrease. However, questions remain among others on how NM is associated with PD and how it is synthesized. The biosynthesis pathway of NM in the human brain has been controversial because the presence of tyrosinase in CA neurons in the SN and LC has been elusive. We propose the following NM synthesis pathway in these CA neurons: (1) Tyrosine is converted by tyrosine hydroxylase (TH) to L-3,4-dihydroxyphenylalanine (L-DOPA), which is converted by aromatic L-amino acid decarboxylase to DA, which in LC neurons is converted by dopamine β-hydroxylase to NE; (2) DA or NE is autoxidized to dopamine quinone (DAQ) or norepinephrine quinone (NEQ); and (3) DAQ or NEQ is converted to eumelanic NM (euNM) and pheomelanic NM (pheoNM) in the absence and presence of cysteine, respectively. This process involves proteins as cysteine source and iron. We also discuss whether the NM amounts per neuromelanin-positive (NM+) CA neuron are higher in PD brain, whether NM quantitatively correlates with neurodegeneration, and whether an active lifestyle may reduce NM formation.
Druh dokumentu: Article
Other literature type
Jazyk: English
ISSN: 1435-1463
0300-9564
DOI: 10.1007/s00702-023-02617-6
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/36939908
Rights: CC BY
URL: http://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/) .
Přístupové číslo: edsair.doi.dedup.....c50c305b32ba0df2cfc692e29d713aa1
Databáze: OpenAIRE
Popis
Abstrakt:The dark pigment neuromelanin (NM) is abundant in cell bodies of dopamine (DA) neurons in the substantia nigra (SN) and norepinephrine (NE) neurons in the locus coeruleus (LC) in the human brain. During the progression of Parkinson’s disease (PD), together with the degeneration of the respective catecholamine (CA) neurons, the NM levels in the SN and LC markedly decrease. However, questions remain among others on how NM is associated with PD and how it is synthesized. The biosynthesis pathway of NM in the human brain has been controversial because the presence of tyrosinase in CA neurons in the SN and LC has been elusive. We propose the following NM synthesis pathway in these CA neurons: (1) Tyrosine is converted by tyrosine hydroxylase (TH) to L-3,4-dihydroxyphenylalanine (L-DOPA), which is converted by aromatic L-amino acid decarboxylase to DA, which in LC neurons is converted by dopamine β-hydroxylase to NE; (2) DA or NE is autoxidized to dopamine quinone (DAQ) or norepinephrine quinone (NEQ); and (3) DAQ or NEQ is converted to eumelanic NM (euNM) and pheomelanic NM (pheoNM) in the absence and presence of cysteine, respectively. This process involves proteins as cysteine source and iron. We also discuss whether the NM amounts per neuromelanin-positive (NM+) CA neuron are higher in PD brain, whether NM quantitatively correlates with neurodegeneration, and whether an active lifestyle may reduce NM formation.
ISSN:14351463
03009564
DOI:10.1007/s00702-023-02617-6