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

Huang Ju Tu, Chih Jou Su, Chao Shiang Peng, Tony Eight Lin, Wei Chun Huang Fu, Kai Cheng Hsu, Tsong Long Hwang, Shiow Lin Pan

研究成果: 雜誌貢獻文章同行評審

8 引文 斯高帕斯(Scopus)

摘要

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 Ab. 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.
原文英語
文章編號12
頁(從 - 到)358-370
頁數13
期刊Journal of Food and Drug Analysis
31
發行號2
DOIs
出版狀態已發佈 - 2023

ASJC Scopus subject areas

  • 食品科學
  • 藥理

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