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Drosophila Ubiquitin C-Terminal Hydrolase Knockdown Model of Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. Many factors have been shown to contribute to its pathogenesis including genetic and environmental factors. Ubiquitin C-terminal hydrolase L1 (UCHL1) is also known to be involved in the pathogenesis of PD. We he...

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Autores principales: Tran, Hiep H., Dang, Suong N. A., Nguyen, Thanh T., Huynh, Anh M., Dao, Linh. M., Kamei, Kaeko, Yamaguchi, Masamitsu, Dang, Thao T. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849740/
https://www.ncbi.nlm.nih.gov/pubmed/29535397
http://dx.doi.org/10.1038/s41598-018-22804-w
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author Tran, Hiep H.
Dang, Suong N. A.
Nguyen, Thanh T.
Huynh, Anh M.
Dao, Linh. M.
Kamei, Kaeko
Yamaguchi, Masamitsu
Dang, Thao T. P.
author_facet Tran, Hiep H.
Dang, Suong N. A.
Nguyen, Thanh T.
Huynh, Anh M.
Dao, Linh. M.
Kamei, Kaeko
Yamaguchi, Masamitsu
Dang, Thao T. P.
author_sort Tran, Hiep H.
collection PubMed
description Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. Many factors have been shown to contribute to its pathogenesis including genetic and environmental factors. Ubiquitin C-terminal hydrolase L1 (UCHL1) is also known to be involved in the pathogenesis of PD. We herein modeled the study of UCHL1 in Drosophila melanogaster and investigated its functions in PD. The specific knockdown of the Drosophila ortholog of UCHL1 (dUCH) in dopaminergic neurons (DA neurons) led to the underdevelopment and/or degeneration of these neurons, specifically in DL1 DA neuron cluster in the larval brain lobe and PPM2, PPM3, PPL2ab, and VUM DA neuron clusters in the adult brain. These defects were followed by a shortage of dopamine in the brain, which subsequently resulted in locomotor dysfunction. The degeneration of DA neurons in dUCH knockdown adult brain, which occurred progressively and severely during the course of aging, mimics the epidemiology of PD. DA neuron and locomotor defects were rescued when dUCH knockdown flies were treated with vitamin C, a well-known antioxidant. These results suggest that dUCH knockdown fly is a promising model for studying the pathogenesis and epidemiology of PD as well as the screening of potential antioxidants for PD therapeutics.
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spelling pubmed-58497402018-03-21 Drosophila Ubiquitin C-Terminal Hydrolase Knockdown Model of Parkinson’s Disease Tran, Hiep H. Dang, Suong N. A. Nguyen, Thanh T. Huynh, Anh M. Dao, Linh. M. Kamei, Kaeko Yamaguchi, Masamitsu Dang, Thao T. P. Sci Rep Article Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. Many factors have been shown to contribute to its pathogenesis including genetic and environmental factors. Ubiquitin C-terminal hydrolase L1 (UCHL1) is also known to be involved in the pathogenesis of PD. We herein modeled the study of UCHL1 in Drosophila melanogaster and investigated its functions in PD. The specific knockdown of the Drosophila ortholog of UCHL1 (dUCH) in dopaminergic neurons (DA neurons) led to the underdevelopment and/or degeneration of these neurons, specifically in DL1 DA neuron cluster in the larval brain lobe and PPM2, PPM3, PPL2ab, and VUM DA neuron clusters in the adult brain. These defects were followed by a shortage of dopamine in the brain, which subsequently resulted in locomotor dysfunction. The degeneration of DA neurons in dUCH knockdown adult brain, which occurred progressively and severely during the course of aging, mimics the epidemiology of PD. DA neuron and locomotor defects were rescued when dUCH knockdown flies were treated with vitamin C, a well-known antioxidant. These results suggest that dUCH knockdown fly is a promising model for studying the pathogenesis and epidemiology of PD as well as the screening of potential antioxidants for PD therapeutics. Nature Publishing Group UK 2018-03-13 /pmc/articles/PMC5849740/ /pubmed/29535397 http://dx.doi.org/10.1038/s41598-018-22804-w Text en © The Author(s) 2018 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Tran, Hiep H.
Dang, Suong N. A.
Nguyen, Thanh T.
Huynh, Anh M.
Dao, Linh. M.
Kamei, Kaeko
Yamaguchi, Masamitsu
Dang, Thao T. P.
Drosophila Ubiquitin C-Terminal Hydrolase Knockdown Model of Parkinson’s Disease
title Drosophila Ubiquitin C-Terminal Hydrolase Knockdown Model of Parkinson’s Disease
title_full Drosophila Ubiquitin C-Terminal Hydrolase Knockdown Model of Parkinson’s Disease
title_fullStr Drosophila Ubiquitin C-Terminal Hydrolase Knockdown Model of Parkinson’s Disease
title_full_unstemmed Drosophila Ubiquitin C-Terminal Hydrolase Knockdown Model of Parkinson’s Disease
title_short Drosophila Ubiquitin C-Terminal Hydrolase Knockdown Model of Parkinson’s Disease
title_sort drosophila ubiquitin c-terminal hydrolase knockdown model of parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849740/
https://www.ncbi.nlm.nih.gov/pubmed/29535397
http://dx.doi.org/10.1038/s41598-018-22804-w
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