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ATP Maintenance via Two Types of ATP Regulators Mitigates Pathological Phenotypes in Mouse Models of Parkinson's Disease
Parkinson's disease is assumed to be caused by mitochondrial dysfunction in the affected dopaminergic neurons in the brain. We have recently created small chemicals, KUSs (Kyoto University Substances), which can reduce cellular ATP consumption. By contrast, agonistic ligands of ERRs (estrogen r...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552266/ https://www.ncbi.nlm.nih.gov/pubmed/28780078 http://dx.doi.org/10.1016/j.ebiom.2017.07.024 |
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author | Nakano, Masaki Imamura, Hiromi Sasaoka, Norio Yamamoto, Masamichi Uemura, Norihito Shudo, Toshiyuki Fuchigami, Tomohiro Takahashi, Ryosuke Kakizuka, Akira |
author_facet | Nakano, Masaki Imamura, Hiromi Sasaoka, Norio Yamamoto, Masamichi Uemura, Norihito Shudo, Toshiyuki Fuchigami, Tomohiro Takahashi, Ryosuke Kakizuka, Akira |
author_sort | Nakano, Masaki |
collection | PubMed |
description | Parkinson's disease is assumed to be caused by mitochondrial dysfunction in the affected dopaminergic neurons in the brain. We have recently created small chemicals, KUSs (Kyoto University Substances), which can reduce cellular ATP consumption. By contrast, agonistic ligands of ERRs (estrogen receptor-related receptors) are expected to raise cellular ATP levels via enhancing ATP production. Here, we show that esculetin functions as an ERR agonist, and its addition to culture media enhances glycolysis and mitochondrial respiration, leading to elevated cellular ATP levels. Subsequently, we show the neuroprotective efficacies of KUSs, esculetin, and GSK4716 (an ERRγ agonist) against cell death in Parkinson's disease models. In the surviving neurons, ATP levels and expression levels of α-synuclein and CHOP (an ER stress-mediated cell death executor) were all rectified. We propose that maintenance of ATP levels, by inhibiting ATP consumption or enhancing ATP production, or both, would be a promising therapeutic strategy for Parkinson's disease. |
format | Online Article Text |
id | pubmed-5552266 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-55522662017-08-22 ATP Maintenance via Two Types of ATP Regulators Mitigates Pathological Phenotypes in Mouse Models of Parkinson's Disease Nakano, Masaki Imamura, Hiromi Sasaoka, Norio Yamamoto, Masamichi Uemura, Norihito Shudo, Toshiyuki Fuchigami, Tomohiro Takahashi, Ryosuke Kakizuka, Akira EBioMedicine Research Paper Parkinson's disease is assumed to be caused by mitochondrial dysfunction in the affected dopaminergic neurons in the brain. We have recently created small chemicals, KUSs (Kyoto University Substances), which can reduce cellular ATP consumption. By contrast, agonistic ligands of ERRs (estrogen receptor-related receptors) are expected to raise cellular ATP levels via enhancing ATP production. Here, we show that esculetin functions as an ERR agonist, and its addition to culture media enhances glycolysis and mitochondrial respiration, leading to elevated cellular ATP levels. Subsequently, we show the neuroprotective efficacies of KUSs, esculetin, and GSK4716 (an ERRγ agonist) against cell death in Parkinson's disease models. In the surviving neurons, ATP levels and expression levels of α-synuclein and CHOP (an ER stress-mediated cell death executor) were all rectified. We propose that maintenance of ATP levels, by inhibiting ATP consumption or enhancing ATP production, or both, would be a promising therapeutic strategy for Parkinson's disease. Elsevier 2017-07-25 /pmc/articles/PMC5552266/ /pubmed/28780078 http://dx.doi.org/10.1016/j.ebiom.2017.07.024 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Paper Nakano, Masaki Imamura, Hiromi Sasaoka, Norio Yamamoto, Masamichi Uemura, Norihito Shudo, Toshiyuki Fuchigami, Tomohiro Takahashi, Ryosuke Kakizuka, Akira ATP Maintenance via Two Types of ATP Regulators Mitigates Pathological Phenotypes in Mouse Models of Parkinson's Disease |
title | ATP Maintenance via Two Types of ATP Regulators Mitigates Pathological Phenotypes in Mouse Models of Parkinson's Disease |
title_full | ATP Maintenance via Two Types of ATP Regulators Mitigates Pathological Phenotypes in Mouse Models of Parkinson's Disease |
title_fullStr | ATP Maintenance via Two Types of ATP Regulators Mitigates Pathological Phenotypes in Mouse Models of Parkinson's Disease |
title_full_unstemmed | ATP Maintenance via Two Types of ATP Regulators Mitigates Pathological Phenotypes in Mouse Models of Parkinson's Disease |
title_short | ATP Maintenance via Two Types of ATP Regulators Mitigates Pathological Phenotypes in Mouse Models of Parkinson's Disease |
title_sort | atp maintenance via two types of atp regulators mitigates pathological phenotypes in mouse models of parkinson's disease |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552266/ https://www.ncbi.nlm.nih.gov/pubmed/28780078 http://dx.doi.org/10.1016/j.ebiom.2017.07.024 |
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