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- Title
Urolithin A exhibits a neuroprotective effect against Alzheimer's disease by inhibiting DYRK1A activity.
- Authors
Huang-Ju Tu; Chih-Jou Su; Chao-Shiang Peng; Tony Eight Lin; Wei-Chun HuangFu; Kai-Cheng Hsu; Tsong-Long Hwang; Shiow-Lin Pan
- 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.
- Subjects
PROTEIN kinases; REVERSE transcriptase polymerase chain reaction; ALZHEIMER'S disease; NEURONS; ANIMAL experimentation; WESTERN immunoblotting; ONE-way analysis of variance; TREATMENT effectiveness; PRIMATES; CELL survival; BENZOPYRANS; PROTEIN-tyrosine kinases; NEUROPROTECTIVE agents; DESCRIPTIVE statistics; RESEARCH funding; MOLECULAR structure; COMPUTER-assisted molecular modeling; DATA analysis software; MICE; PHARMACODYNAMICS
- Publication
Journal of Food & Drug Analysis, 2023, Vol 31, Issue 2, p358
- ISSN
1021-9498
- Publication type
Article
- DOI
10.38212/2224-6614.3462