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

Huang-Ju Tu, Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, No.250, Wu-Xing Street, Xinyi Dist., Taipei 110, Taiwan
Chih-Jou Su, Ph.D. program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, No.250, Wu-Xing Street, Xinyi Dist., Taipei 110, Taiwan
Chao-Shiang Peng, Ph.D. program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, No.250, Wu-Xing Street, Xinyi Dist., Taipei 110, Taiwan
Tony Eight Lin, Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, No.250, Wu-Xing Street, Xinyi Dist., Taipei 110, Taiwan
Wei-Chun Huang Fu, Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, No.250, Wu-Xing Street, Xinyi Dist., Taipei 110, Taiwan
Kai-Cheng Hsu, Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, No.250, Wu-Xing Street, Xinyi Dist., Taipei 110, Taiwan
Tsong-Long Hwang, Graduate Institute of Natural Products, College of Medicine, Chang Gung University, No.259, Wenhua 1st Rd., Guishan Dist., Taoyuan City 333, Taiwan
Shiow-Lin Pan, Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, No.250, Wu-Xing Street, Xinyi Dist., Taipei 110, TaiwanFollow

Abstract

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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Recommended Citation

Tu, Huang-Ju; Su, Chih-Jou; Peng, Chao-Shiang; Lin, Tony Eight; Huang Fu, Wei-Chun; Hsu, Kai-Cheng; Hwang, Tsong-Long; and Pan, Shiow-Lin (2023) "Urolithin A exhibits a neuroprotective effect against Alzheimer’s disease by inhibiting DYRK1A activity," Journal of Food and Drug Analysis: Vol. 31 : Iss. 2 , Article 12.
Available at: https://doi.org/10.38212/2224-6614.3462