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Functional Modulators of Resilience to Age-Associated Dopaminergic Neurodegeneration in C. elegans
The societal costs of neurodegenerative diseases demand a sense of urgency and innovative strategies toward therapeutic intervention. We have exploited the experimental attributes of roundworm, C. elegans, as a model to expedite discovery of genetic and chemical modifiers of the age-dependent progre...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Oxford University Press
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7742646/ http://dx.doi.org/10.1093/geroni/igaa057.2635 |
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author | Caldwell, Guy |
author_facet | Caldwell, Guy |
author_sort | Caldwell, Guy |
collection | PubMed |
description | The societal costs of neurodegenerative diseases demand a sense of urgency and innovative strategies toward therapeutic intervention. We have exploited the experimental attributes of roundworm, C. elegans, as a model to expedite discovery of genetic and chemical modifiers of the age-dependent progressive neurodegeneration of dopaminergic neurons commonly associated with Parkinson’s disease (PD). Our model of transgenic nematodes overexpressing the misfolding-prone familial PD gene product, alpha-synuclein, has proven prescient in illuminating key aspects of PD pathology, including vesicular trafficking, autophagy, stress response, lipid dynamics, as well as the first evidence of endolysosomal function in effecting dopaminergic neurodegeneration. Subsequent chemical-genetic analyses reveal a mechanism whereby dopamine transport intersects with epigenetic control of gene expression through proteins functioning in endocytic regulation to modulate neuroprotection. We theorize this reflects a “tunable” nexus of gene-by-environmental regulation where dopamine levels, which impact alpha-synuclein misfolding, are coordinately controlled with epigenetic response to mediate resilience to age-dependent neurodegeneration. |
format | Online Article Text |
id | pubmed-7742646 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77426462020-12-21 Functional Modulators of Resilience to Age-Associated Dopaminergic Neurodegeneration in C. elegans Caldwell, Guy Innov Aging Abstracts The societal costs of neurodegenerative diseases demand a sense of urgency and innovative strategies toward therapeutic intervention. We have exploited the experimental attributes of roundworm, C. elegans, as a model to expedite discovery of genetic and chemical modifiers of the age-dependent progressive neurodegeneration of dopaminergic neurons commonly associated with Parkinson’s disease (PD). Our model of transgenic nematodes overexpressing the misfolding-prone familial PD gene product, alpha-synuclein, has proven prescient in illuminating key aspects of PD pathology, including vesicular trafficking, autophagy, stress response, lipid dynamics, as well as the first evidence of endolysosomal function in effecting dopaminergic neurodegeneration. Subsequent chemical-genetic analyses reveal a mechanism whereby dopamine transport intersects with epigenetic control of gene expression through proteins functioning in endocytic regulation to modulate neuroprotection. We theorize this reflects a “tunable” nexus of gene-by-environmental regulation where dopamine levels, which impact alpha-synuclein misfolding, are coordinately controlled with epigenetic response to mediate resilience to age-dependent neurodegeneration. Oxford University Press 2020-12-16 /pmc/articles/PMC7742646/ http://dx.doi.org/10.1093/geroni/igaa057.2635 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Abstracts Caldwell, Guy Functional Modulators of Resilience to Age-Associated Dopaminergic Neurodegeneration in C. elegans |
title | Functional Modulators of Resilience to Age-Associated Dopaminergic Neurodegeneration in C. elegans |
title_full | Functional Modulators of Resilience to Age-Associated Dopaminergic Neurodegeneration in C. elegans |
title_fullStr | Functional Modulators of Resilience to Age-Associated Dopaminergic Neurodegeneration in C. elegans |
title_full_unstemmed | Functional Modulators of Resilience to Age-Associated Dopaminergic Neurodegeneration in C. elegans |
title_short | Functional Modulators of Resilience to Age-Associated Dopaminergic Neurodegeneration in C. elegans |
title_sort | functional modulators of resilience to age-associated dopaminergic neurodegeneration in c. elegans |
topic | Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7742646/ http://dx.doi.org/10.1093/geroni/igaa057.2635 |
work_keys_str_mv | AT caldwellguy functionalmodulatorsofresiliencetoageassociateddopaminergicneurodegenerationincelegans |