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Found in Translation: The Utility of C. elegans Alpha-Synuclein Models of Parkinson’s Disease

Parkinson’s Disease (PD) is the second-most common neurodegenerative disease in the world, yet the fundamental and underlying causes of the disease are largely unknown, and treatments remain sparse and impotent. Several biological systems have been employed to model the disease but the nematode roun...

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Autores principales: Gaeta, Anthony L., Caldwell, Kim A., Caldwell, Guy A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523935/
https://www.ncbi.nlm.nih.gov/pubmed/30925741
http://dx.doi.org/10.3390/brainsci9040073
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author Gaeta, Anthony L.
Caldwell, Kim A.
Caldwell, Guy A.
author_facet Gaeta, Anthony L.
Caldwell, Kim A.
Caldwell, Guy A.
author_sort Gaeta, Anthony L.
collection PubMed
description Parkinson’s Disease (PD) is the second-most common neurodegenerative disease in the world, yet the fundamental and underlying causes of the disease are largely unknown, and treatments remain sparse and impotent. Several biological systems have been employed to model the disease but the nematode roundworm Caenorhabditis elegans (C. elegans) shows unique promise among these to disinter the elusive factors that may prevent, halt, and/or reverse PD phenotypes. Some of the most salient of these C. elegans models of PD are those that position the misfolding-prone protein alpha-synuclein (α-syn), a hallmark pathological component of PD, as the primary target for scientific interrogation. By transgenic expression of human α-syn in different tissues, including dopamine neurons and muscle cells, the primary cellular phenotypes of PD in humans have been recapitulated in these C. elegans models and have already uncovered multifarious genetic factors and chemical compounds that attenuate dopaminergic neurodegeneration. This review describes the paramount discoveries obtained through the application of different α-syn models of PD in C. elegans and highlights their established utility and respective promise to successfully uncover new conserved genetic modifiers, functional mechanisms, therapeutic targets and molecular leads for PD with the potential to translate to humans.
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spelling pubmed-65239352019-06-03 Found in Translation: The Utility of C. elegans Alpha-Synuclein Models of Parkinson’s Disease Gaeta, Anthony L. Caldwell, Kim A. Caldwell, Guy A. Brain Sci Review Parkinson’s Disease (PD) is the second-most common neurodegenerative disease in the world, yet the fundamental and underlying causes of the disease are largely unknown, and treatments remain sparse and impotent. Several biological systems have been employed to model the disease but the nematode roundworm Caenorhabditis elegans (C. elegans) shows unique promise among these to disinter the elusive factors that may prevent, halt, and/or reverse PD phenotypes. Some of the most salient of these C. elegans models of PD are those that position the misfolding-prone protein alpha-synuclein (α-syn), a hallmark pathological component of PD, as the primary target for scientific interrogation. By transgenic expression of human α-syn in different tissues, including dopamine neurons and muscle cells, the primary cellular phenotypes of PD in humans have been recapitulated in these C. elegans models and have already uncovered multifarious genetic factors and chemical compounds that attenuate dopaminergic neurodegeneration. This review describes the paramount discoveries obtained through the application of different α-syn models of PD in C. elegans and highlights their established utility and respective promise to successfully uncover new conserved genetic modifiers, functional mechanisms, therapeutic targets and molecular leads for PD with the potential to translate to humans. MDPI 2019-03-28 /pmc/articles/PMC6523935/ /pubmed/30925741 http://dx.doi.org/10.3390/brainsci9040073 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Gaeta, Anthony L.
Caldwell, Kim A.
Caldwell, Guy A.
Found in Translation: The Utility of C. elegans Alpha-Synuclein Models of Parkinson’s Disease
title Found in Translation: The Utility of C. elegans Alpha-Synuclein Models of Parkinson’s Disease
title_full Found in Translation: The Utility of C. elegans Alpha-Synuclein Models of Parkinson’s Disease
title_fullStr Found in Translation: The Utility of C. elegans Alpha-Synuclein Models of Parkinson’s Disease
title_full_unstemmed Found in Translation: The Utility of C. elegans Alpha-Synuclein Models of Parkinson’s Disease
title_short Found in Translation: The Utility of C. elegans Alpha-Synuclein Models of Parkinson’s Disease
title_sort found in translation: the utility of c. elegans alpha-synuclein models of parkinson’s disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523935/
https://www.ncbi.nlm.nih.gov/pubmed/30925741
http://dx.doi.org/10.3390/brainsci9040073
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