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 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.

Automated summary

Alzheimer's disease (AD) affects more than 50 million people worldwide, but current drugs are not effective in improving cognitive impairment in AD patients. Urolithin A (UA), obtained from ellagic acid and ellagitannin, has been found to have neuroprotective effects in AD animal models. This study reveals that UA inhibits the activity of DYRK1A, a protein associated with AD, and improves memory impairment in an AD-like mouse model. These findings suggest that UA could be a potential therapeutic option for AD patients.