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Modeling Parkinson’s Disease in C. elegans

Parkinson’s disease (PD) is an adult onset neurodegenerative disease that is characterized by selective degeneration of neurons primarily in the substantia nigra. At present, the pathogenesis of PD is incompletely understood and there are no neuroprotective treatments available. Accurate animal mode...

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Autores principales: Cooper, Jason F., Van Raamsdonk, Jeremy M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836411/
https://www.ncbi.nlm.nih.gov/pubmed/29480229
http://dx.doi.org/10.3233/JPD-171258
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author Cooper, Jason F.
Van Raamsdonk, Jeremy M.
author_facet Cooper, Jason F.
Van Raamsdonk, Jeremy M.
author_sort Cooper, Jason F.
collection PubMed
description Parkinson’s disease (PD) is an adult onset neurodegenerative disease that is characterized by selective degeneration of neurons primarily in the substantia nigra. At present, the pathogenesis of PD is incompletely understood and there are no neuroprotective treatments available. Accurate animal models of PD provide the opportunity to elucidate disease mechanisms and identify therapeutic targets. This review focuses on C. elegans models of PD, including both genetic and toxicant models. This microscopic worm offers several advantages for the study of PD including ease of genetic manipulation, ability to complete experiments rapidly, low cost, and ability to perform large scale screens for disease modifiers. A number of C. elegans models of PD have been generated including transgenic worms that express α-synuclein or LRRK2, and worms with deletions in PRKN/pdr-1, PINK1/pink-1, DJ-1/djr-1.1/djr-1.2 and ATP13A2/catp-6. These worms have been shown to exhibit multiple phenotypic deficits including the loss of dopamine neurons, disruption of dopamine-dependent behaviors, increased sensitivity to stress, age-dependent aggregation, and deficits in movement. As a result, these phenotypes can be used as outcome measures to gain insight into disease pathogenesis and to identify disease modifiers. In this way, C. elegans can be used as an experimental tool to elucidate mechanisms involved in PD and to find novel therapeutic targets that can subsequently be validated in other models.
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spelling pubmed-58364112018-03-12 Modeling Parkinson’s Disease in C. elegans Cooper, Jason F. Van Raamsdonk, Jeremy M. J Parkinsons Dis Review Parkinson’s disease (PD) is an adult onset neurodegenerative disease that is characterized by selective degeneration of neurons primarily in the substantia nigra. At present, the pathogenesis of PD is incompletely understood and there are no neuroprotective treatments available. Accurate animal models of PD provide the opportunity to elucidate disease mechanisms and identify therapeutic targets. This review focuses on C. elegans models of PD, including both genetic and toxicant models. This microscopic worm offers several advantages for the study of PD including ease of genetic manipulation, ability to complete experiments rapidly, low cost, and ability to perform large scale screens for disease modifiers. A number of C. elegans models of PD have been generated including transgenic worms that express α-synuclein or LRRK2, and worms with deletions in PRKN/pdr-1, PINK1/pink-1, DJ-1/djr-1.1/djr-1.2 and ATP13A2/catp-6. These worms have been shown to exhibit multiple phenotypic deficits including the loss of dopamine neurons, disruption of dopamine-dependent behaviors, increased sensitivity to stress, age-dependent aggregation, and deficits in movement. As a result, these phenotypes can be used as outcome measures to gain insight into disease pathogenesis and to identify disease modifiers. In this way, C. elegans can be used as an experimental tool to elucidate mechanisms involved in PD and to find novel therapeutic targets that can subsequently be validated in other models. IOS Press 2018-02-17 /pmc/articles/PMC5836411/ /pubmed/29480229 http://dx.doi.org/10.3233/JPD-171258 Text en © 2018 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Cooper, Jason F.
Van Raamsdonk, Jeremy M.
Modeling Parkinson’s Disease in C. elegans
title Modeling Parkinson’s Disease in C. elegans
title_full Modeling Parkinson’s Disease in C. elegans
title_fullStr Modeling Parkinson’s Disease in C. elegans
title_full_unstemmed Modeling Parkinson’s Disease in C. elegans
title_short Modeling Parkinson’s Disease in C. elegans
title_sort modeling parkinson’s disease in c. elegans
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836411/
https://www.ncbi.nlm.nih.gov/pubmed/29480229
http://dx.doi.org/10.3233/JPD-171258
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