Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Nagatsu, Toshiharu, Nakashima, Akira, Watanabe, Hirohisa, Ito, Shosuke, Wakamatsu, Kazumasa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784691909433753600
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
work_keys_str_mv AT nagatsutoshiharu neuromelanininparkinsonsdiseasetyrosinehydroxylaseandtyrosinase
AT nakashimaakira neuromelanininparkinsonsdiseasetyrosinehydroxylaseandtyrosinase
AT watanabehirohisa neuromelanininparkinsonsdiseasetyrosinehydroxylaseandtyrosinase
AT itoshosuke neuromelanininparkinsonsdiseasetyrosinehydroxylaseandtyrosinase
AT wakamatsukazumasa neuromelanininparkinsonsdiseasetyrosinehydroxylaseandtyrosinase