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Urolithin A exhibits a neuroprotective effect against Alzheimer’s disease by inhibiting DYRK1A activity

Alzheimer’s disease (AD) is a devastating neurodegenerative disease with more than 50 million people suffer from it. Unfortunately, none of the currently available drugs is able to improve cognitive impairment in AD patients. Urolithin A (UA) is a metabolite obtained from ellagic acid and ellagitann...

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Autores principales: Tu, Huang-Ju, Su, Chih-Jou, Peng, Chao-Shiang, Lin, Tony Eight, HuangFu, Wei-Chun, Hsu, Kai-Cheng, Hwang, Tsong-Long, Pan, Shiow-Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taiwan Food and Drug Administration 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281726/
https://www.ncbi.nlm.nih.gov/pubmed/37335158
http://dx.doi.org/10.38212/2224-6614.3462
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author Tu, Huang-Ju
Su, Chih-Jou
Peng, Chao-Shiang
Lin, Tony Eight
HuangFu, Wei-Chun
Hsu, Kai-Cheng
Hwang, Tsong-Long
Pan, Shiow-Lin
author_facet Tu, Huang-Ju
Su, Chih-Jou
Peng, Chao-Shiang
Lin, Tony Eight
HuangFu, Wei-Chun
Hsu, Kai-Cheng
Hwang, Tsong-Long
Pan, Shiow-Lin
author_sort Tu, Huang-Ju
collection PubMed
description Alzheimer’s disease (AD) is a devastating neurodegenerative disease with more than 50 million people suffer from it. Unfortunately, none of the currently available drugs is able to improve cognitive impairment in AD patients. Urolithin A (UA) is a metabolite obtained from ellagic acid and ellagitannin through the intestinal flora, and it has antioxidant and anti-inflammatory properties. Previous reports found that UA had neuroprotective effects in an AD animal model, but the detailed mechanism still needs to be elucidated. In this study, we performed kinase-profiling to show that dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is the main target of UA. Studies showed that the level of DYRK1A in AD patients’ brains was higher than that of healthy people, and it was closely related to the occurrence and progression of AD. Our results revealed that UA significantly reduced the activity of DYRK1A, which led to de-phosphorylation of tau and further stabilized microtubule polymerization. UA also provided neuroprotective effects by inhibiting the production of inflammatory cytokines caused by Aβ. We further showed that UA significantly improved memory impairment in an AD-like mouse model. In summary, our results indicate that UA is a DYRK1A inhibitor that may provide therapeutic advantages for AD patients.
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spelling pubmed-102817262023-06-21 Urolithin A exhibits a neuroprotective effect against Alzheimer’s disease by inhibiting DYRK1A activity Tu, Huang-Ju Su, Chih-Jou Peng, Chao-Shiang Lin, Tony Eight HuangFu, Wei-Chun Hsu, Kai-Cheng Hwang, Tsong-Long Pan, Shiow-Lin J Food Drug Anal Original Article Alzheimer’s disease (AD) is a devastating neurodegenerative disease with more than 50 million people suffer from it. Unfortunately, none of the currently available drugs is able to improve cognitive impairment in AD patients. Urolithin A (UA) is a metabolite obtained from ellagic acid and ellagitannin through the intestinal flora, and it has antioxidant and anti-inflammatory properties. Previous reports found that UA had neuroprotective effects in an AD animal model, but the detailed mechanism still needs to be elucidated. In this study, we performed kinase-profiling to show that dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is the main target of UA. Studies showed that the level of DYRK1A in AD patients’ brains was higher than that of healthy people, and it was closely related to the occurrence and progression of AD. Our results revealed that UA significantly reduced the activity of DYRK1A, which led to de-phosphorylation of tau and further stabilized microtubule polymerization. UA also provided neuroprotective effects by inhibiting the production of inflammatory cytokines caused by Aβ. We further showed that UA significantly improved memory impairment in an AD-like mouse model. In summary, our results indicate that UA is a DYRK1A inhibitor that may provide therapeutic advantages for AD patients. Taiwan Food and Drug Administration 2023-06-15 /pmc/articles/PMC10281726/ /pubmed/37335158 http://dx.doi.org/10.38212/2224-6614.3462 Text en © 2023 Taiwan Food and Drug Administration https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Original Article
Tu, Huang-Ju
Su, Chih-Jou
Peng, Chao-Shiang
Lin, Tony Eight
HuangFu, Wei-Chun
Hsu, Kai-Cheng
Hwang, Tsong-Long
Pan, Shiow-Lin
Urolithin A exhibits a neuroprotective effect against Alzheimer’s disease by inhibiting DYRK1A activity
title Urolithin A exhibits a neuroprotective effect against Alzheimer’s disease by inhibiting DYRK1A activity
title_full Urolithin A exhibits a neuroprotective effect against Alzheimer’s disease by inhibiting DYRK1A activity
title_fullStr Urolithin A exhibits a neuroprotective effect against Alzheimer’s disease by inhibiting DYRK1A activity
title_full_unstemmed Urolithin A exhibits a neuroprotective effect against Alzheimer’s disease by inhibiting DYRK1A activity
title_short Urolithin A exhibits a neuroprotective effect against Alzheimer’s disease by inhibiting DYRK1A activity
title_sort urolithin a exhibits a neuroprotective effect against alzheimer’s disease by inhibiting dyrk1a activity
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281726/
https://www.ncbi.nlm.nih.gov/pubmed/37335158
http://dx.doi.org/10.38212/2224-6614.3462
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