Esculetin Provides Neuroprotection against Mutant Huntingtin-Induced Toxicity in Huntington’s Disease Models
Huntington’s disease (HD) is a neurodegenerative disorder caused by an abnormal CAG trinucleotide repeat expansion within exon 1 of the huntingtin (HTT) gene. This mutation leads to the production of mutant HTT (mHTT) protein which triggers neuronal death through several mechanisms. Here, we investi...
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MDPI AG
2021-10-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/10/1044 |
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| author | Letizia Pruccoli Carlo Breda Gabriella Teti Mirella Falconi Flaviano Giorgini Andrea Tarozzi |
| author_facet | Letizia Pruccoli Carlo Breda Gabriella Teti Mirella Falconi Flaviano Giorgini Andrea Tarozzi |
| author_sort | Letizia Pruccoli |
| collection | DOAJ |
| description | Huntington’s disease (HD) is a neurodegenerative disorder caused by an abnormal CAG trinucleotide repeat expansion within exon 1 of the huntingtin (HTT) gene. This mutation leads to the production of mutant HTT (mHTT) protein which triggers neuronal death through several mechanisms. Here, we investigated the neuroprotective effects of esculetin (ESC), a bioactive phenolic compound, in an inducible PC12 model and a transgenic <i>Drosophila melanogaster</i> model of HD, both of which express mHTT fragments. ESC partially inhibited the progression of mHTT aggregation and reduced neuronal death through its ability to counteract the oxidative stress and mitochondria impairment elicited by mHTT in the PC12 model. The ability of ESC to counteract neuronal death was also confirmed in the transgenic <i>Drosophila</i> model. Although ESC did not modify the lifespan of the transgenic <i>Drosophila</i>, it still seemed to have a positive impact on the HD phenotype of this model. Based on our findings, ESC may be further studied as a potential neuroprotective agent in a rodent transgenic model of HD. |
| first_indexed | 2024-03-10T06:17:38Z |
| format | Article |
| id | doaj.art-d2e5c49caf6742e499ef86890a2aba8f |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T06:17:38Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-d2e5c49caf6742e499ef86890a2aba8f2023-11-22T19:36:37ZengMDPI AGPharmaceuticals1424-82472021-10-011410104410.3390/ph14101044Esculetin Provides Neuroprotection against Mutant Huntingtin-Induced Toxicity in Huntington’s Disease ModelsLetizia Pruccoli0Carlo Breda1Gabriella Teti2Mirella Falconi3Flaviano Giorgini4Andrea Tarozzi5Department for Life Quality Studies, University of Bologna, 47921 Rimini, ItalyDepartment of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UKDepartment of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, ItalyDepartment of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, ItalyDepartment of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UKDepartment for Life Quality Studies, University of Bologna, 47921 Rimini, ItalyHuntington’s disease (HD) is a neurodegenerative disorder caused by an abnormal CAG trinucleotide repeat expansion within exon 1 of the huntingtin (HTT) gene. This mutation leads to the production of mutant HTT (mHTT) protein which triggers neuronal death through several mechanisms. Here, we investigated the neuroprotective effects of esculetin (ESC), a bioactive phenolic compound, in an inducible PC12 model and a transgenic <i>Drosophila melanogaster</i> model of HD, both of which express mHTT fragments. ESC partially inhibited the progression of mHTT aggregation and reduced neuronal death through its ability to counteract the oxidative stress and mitochondria impairment elicited by mHTT in the PC12 model. The ability of ESC to counteract neuronal death was also confirmed in the transgenic <i>Drosophila</i> model. Although ESC did not modify the lifespan of the transgenic <i>Drosophila</i>, it still seemed to have a positive impact on the HD phenotype of this model. Based on our findings, ESC may be further studied as a potential neuroprotective agent in a rodent transgenic model of HD.https://www.mdpi.com/1424-8247/14/10/1044Huntington’s diseasehuntingtinmitochondrial dysfunctionoxidative stressneuroprotectionesculetin |
| spellingShingle | Letizia Pruccoli Carlo Breda Gabriella Teti Mirella Falconi Flaviano Giorgini Andrea Tarozzi Esculetin Provides Neuroprotection against Mutant Huntingtin-Induced Toxicity in Huntington’s Disease Models Pharmaceuticals Huntington’s disease huntingtin mitochondrial dysfunction oxidative stress neuroprotection esculetin |
| title | Esculetin Provides Neuroprotection against Mutant Huntingtin-Induced Toxicity in Huntington’s Disease Models |
| title_full | Esculetin Provides Neuroprotection against Mutant Huntingtin-Induced Toxicity in Huntington’s Disease Models |
| title_fullStr | Esculetin Provides Neuroprotection against Mutant Huntingtin-Induced Toxicity in Huntington’s Disease Models |
| title_full_unstemmed | Esculetin Provides Neuroprotection against Mutant Huntingtin-Induced Toxicity in Huntington’s Disease Models |
| title_short | Esculetin Provides Neuroprotection against Mutant Huntingtin-Induced Toxicity in Huntington’s Disease Models |
| title_sort | esculetin provides neuroprotection against mutant huntingtin induced toxicity in huntington s disease models |
| topic | Huntington’s disease huntingtin mitochondrial dysfunction oxidative stress neuroprotection esculetin |
| url | https://www.mdpi.com/1424-8247/14/10/1044 |
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