Modeling neurodegeneration in Caenorhabditis elegans
The global burden of neurodegenerative diseases underscores the urgent need for innovative strategies to define new drug targets and disease-modifying factors. The nematode Caenorhabditis elegans has served as the experimental subject for multiple transformative discoveries that have redefined our u...
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doaj-662302addb8d4a638a0de89ba91528bc2020-12-23T13:44:09ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112020-10-01131010.1242/dmm.046110046110Modeling neurodegeneration in Caenorhabditis elegansKim A. Caldwell0Corey W. Willicott1Guy A. Caldwell2 Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA The global burden of neurodegenerative diseases underscores the urgent need for innovative strategies to define new drug targets and disease-modifying factors. The nematode Caenorhabditis elegans has served as the experimental subject for multiple transformative discoveries that have redefined our understanding of biology for ∼60 years. More recently, the considerable attributes of C. elegans have been applied to neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease and Huntington's disease. Transgenic nematodes with genes encoding normal and disease variants of proteins at the single- or multi-copy level under neuronal-specific promoters limits expression to select neuronal subtypes. The anatomical transparency of C. elegans affords the use of co-expressed fluorescent proteins to follow the progression of neurodegeneration as the animals age. Significantly, a completely defined connectome facilitates detailed understanding of the impact of neurodegeneration on organismal health and offers a unique capacity to accurately link cell death with behavioral dysfunction or phenotypic variation in vivo. Moreover, chemical treatments, as well as forward and reverse genetic screening, hasten the identification of modifiers that alter neurodegeneration. When combined, these chemical-genetic analyses establish critical threshold states to enhance or reduce cellular stress for dissecting associated pathways. Furthermore, C. elegans can rapidly reveal whether lifespan or healthspan factor into neurodegenerative processes. Here, we outline the methodologies employed to investigate neurodegeneration in C. elegans and highlight numerous studies that exemplify its utility as a pre-clinical intermediary to expedite and inform mammalian translational research.http://dmm.biologists.org/content/13/10/dmm046110agingbehaviorgeneticsmodelingphenotypeproteostasis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kim A. Caldwell Corey W. Willicott Guy A. Caldwell |
spellingShingle |
Kim A. Caldwell Corey W. Willicott Guy A. Caldwell Modeling neurodegeneration in Caenorhabditis elegans Disease Models & Mechanisms aging behavior genetics modeling phenotype proteostasis |
author_facet |
Kim A. Caldwell Corey W. Willicott Guy A. Caldwell |
author_sort |
Kim A. Caldwell |
title |
Modeling neurodegeneration in Caenorhabditis elegans |
title_short |
Modeling neurodegeneration in Caenorhabditis elegans |
title_full |
Modeling neurodegeneration in Caenorhabditis elegans |
title_fullStr |
Modeling neurodegeneration in Caenorhabditis elegans |
title_full_unstemmed |
Modeling neurodegeneration in Caenorhabditis elegans |
title_sort |
modeling neurodegeneration in caenorhabditis elegans |
publisher |
The Company of Biologists |
series |
Disease Models & Mechanisms |
issn |
1754-8403 1754-8411 |
publishDate |
2020-10-01 |
description |
The global burden of neurodegenerative diseases underscores the urgent need for innovative strategies to define new drug targets and disease-modifying factors. The nematode Caenorhabditis elegans has served as the experimental subject for multiple transformative discoveries that have redefined our understanding of biology for ∼60 years. More recently, the considerable attributes of C. elegans have been applied to neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease and Huntington's disease. Transgenic nematodes with genes encoding normal and disease variants of proteins at the single- or multi-copy level under neuronal-specific promoters limits expression to select neuronal subtypes. The anatomical transparency of C. elegans affords the use of co-expressed fluorescent proteins to follow the progression of neurodegeneration as the animals age. Significantly, a completely defined connectome facilitates detailed understanding of the impact of neurodegeneration on organismal health and offers a unique capacity to accurately link cell death with behavioral dysfunction or phenotypic variation in vivo. Moreover, chemical treatments, as well as forward and reverse genetic screening, hasten the identification of modifiers that alter neurodegeneration. When combined, these chemical-genetic analyses establish critical threshold states to enhance or reduce cellular stress for dissecting associated pathways. Furthermore, C. elegans can rapidly reveal whether lifespan or healthspan factor into neurodegenerative processes. Here, we outline the methodologies employed to investigate neurodegeneration in C. elegans and highlight numerous studies that exemplify its utility as a pre-clinical intermediary to expedite and inform mammalian translational research. |
topic |
aging behavior genetics modeling phenotype proteostasis |
url |
http://dmm.biologists.org/content/13/10/dmm046110 |
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AT kimacaldwell modelingneurodegenerationincaenorhabditiselegans AT coreywwillicott modelingneurodegenerationincaenorhabditiselegans AT guyacaldwell modelingneurodegenerationincaenorhabditiselegans |
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