Geranylgeranylacetone Ameliorates Beta-Amyloid Toxicity and Extends Lifespan via the Heat Shock Response in Caenorhabditis elegans
Activation of a cytoprotective cellular pathway known as the heat shock response (HSR) is a promising strategy for the treatment of Alzheimer’s disease and other neurodegenerative diseases. Geranylgeranylacetone (GGA) is a commonly used anti-ulcer drug in Japan that has been shown to activate the HS...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Aging |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fragi.2022.846977/full |
| _version_ | 1828366572549308416 |
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| author | Isiah Mossiah Sabrina M. Perez Taylor R. Stanley Michaela K. Foley Karen S. Kim Guisbert Eric Guisbert |
| author_facet | Isiah Mossiah Sabrina M. Perez Taylor R. Stanley Michaela K. Foley Karen S. Kim Guisbert Eric Guisbert |
| author_sort | Isiah Mossiah |
| collection | DOAJ |
| description | Activation of a cytoprotective cellular pathway known as the heat shock response (HSR) is a promising strategy for the treatment of Alzheimer’s disease and other neurodegenerative diseases. Geranylgeranylacetone (GGA) is a commonly used anti-ulcer drug in Japan that has been shown to activate the HSR. Here, we establish C. elegans as a model system to investigate the effects of GGA. First, we show that GGA-mediated activation of the HSR is conserved in worms. Then, we show that GGA can ameliorate beta-amyloid toxicity in both muscle and neuronal worm Alzheimer’s disease models. Finally, we find that exposure to GGA is sufficient to extend the lifespan of wild-type worms. Significantly, the beneficial effects of GGA on both beta-amyloid toxicity and lifespan are dependent on HSR activation. Taken together, this research supports further development of GGA as a therapeutic for Alzheimer’s disease, provides evidence that HSR activation is a relevant therapeutic mechanism, and indicates that the beneficial effects of GGA are not limited to disease. |
| first_indexed | 2024-04-14T05:46:54Z |
| format | Article |
| id | doaj.art-a2b9bc031cb8452f95661a3363a39cb9 |
| institution | Directory Open Access Journal |
| issn | 2673-6217 |
| language | English |
| last_indexed | 2024-04-14T05:46:54Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging |
| spelling | doaj.art-a2b9bc031cb8452f95661a3363a39cb92022-12-22T02:09:16ZengFrontiers Media S.A.Frontiers in Aging2673-62172022-04-01310.3389/fragi.2022.846977846977Geranylgeranylacetone Ameliorates Beta-Amyloid Toxicity and Extends Lifespan via the Heat Shock Response in Caenorhabditis elegansIsiah MossiahSabrina M. PerezTaylor R. StanleyMichaela K. FoleyKaren S. Kim GuisbertEric GuisbertActivation of a cytoprotective cellular pathway known as the heat shock response (HSR) is a promising strategy for the treatment of Alzheimer’s disease and other neurodegenerative diseases. Geranylgeranylacetone (GGA) is a commonly used anti-ulcer drug in Japan that has been shown to activate the HSR. Here, we establish C. elegans as a model system to investigate the effects of GGA. First, we show that GGA-mediated activation of the HSR is conserved in worms. Then, we show that GGA can ameliorate beta-amyloid toxicity in both muscle and neuronal worm Alzheimer’s disease models. Finally, we find that exposure to GGA is sufficient to extend the lifespan of wild-type worms. Significantly, the beneficial effects of GGA on both beta-amyloid toxicity and lifespan are dependent on HSR activation. Taken together, this research supports further development of GGA as a therapeutic for Alzheimer’s disease, provides evidence that HSR activation is a relevant therapeutic mechanism, and indicates that the beneficial effects of GGA are not limited to disease.https://www.frontiersin.org/articles/10.3389/fragi.2022.846977/fullgeranylgeranylacetoneHSF1heat shock responseAlzheimer’s diseaseaginglongevity |
| spellingShingle | Isiah Mossiah Sabrina M. Perez Taylor R. Stanley Michaela K. Foley Karen S. Kim Guisbert Eric Guisbert Geranylgeranylacetone Ameliorates Beta-Amyloid Toxicity and Extends Lifespan via the Heat Shock Response in Caenorhabditis elegans Frontiers in Aging geranylgeranylacetone HSF1 heat shock response Alzheimer’s disease aging longevity |
| title | Geranylgeranylacetone Ameliorates Beta-Amyloid Toxicity and Extends Lifespan via the Heat Shock Response in Caenorhabditis elegans |
| title_full | Geranylgeranylacetone Ameliorates Beta-Amyloid Toxicity and Extends Lifespan via the Heat Shock Response in Caenorhabditis elegans |
| title_fullStr | Geranylgeranylacetone Ameliorates Beta-Amyloid Toxicity and Extends Lifespan via the Heat Shock Response in Caenorhabditis elegans |
| title_full_unstemmed | Geranylgeranylacetone Ameliorates Beta-Amyloid Toxicity and Extends Lifespan via the Heat Shock Response in Caenorhabditis elegans |
| title_short | Geranylgeranylacetone Ameliorates Beta-Amyloid Toxicity and Extends Lifespan via the Heat Shock Response in Caenorhabditis elegans |
| title_sort | geranylgeranylacetone ameliorates beta amyloid toxicity and extends lifespan via the heat shock response in caenorhabditis elegans |
| topic | geranylgeranylacetone HSF1 heat shock response Alzheimer’s disease aging longevity |
| url | https://www.frontiersin.org/articles/10.3389/fragi.2022.846977/full |
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