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- W4281647810 abstract "Abstract Serum tyrosine levels increase during aging, neurocognitive, metabolic, and cardiovascular disorders. However, calorie restriction (CR) and sleep lower serum tyrosine levels. We previously showed that tyrosine inhibits tyrosyl-tRNA synthetase (TyrRS)-mediated activation of poly-ADP-ribose polymerase 1 (PARP1). Here, we show that histone serine-ADP-ribosylation is decreased in Alzheimer’s Disease (AD) brains, and increased tyrosine levels deplete TyrRS and cause neuronal DNA damage. However, dopamine and brain-derived neurotrophic factor (BDNF) increase TyrRS and histone serine-ADP-ribosylation. Furthermore, cis -resveratrol ( cis -RSV) that binds to TyrRS mimicking a ‘tyrosine-free’ conformation increases TyrRS, facilitates histone serine-ADP-ribosylation-dependent DNA repair, and provides neuroprotection in a TyrRS-dependent manner. Conversely, trans -RSV that binds to TyrRS mimicking a ‘tyrosine-like’ conformation decreases TyrRS, inhibits serine-ADP-ribosylation-dependent DNA repair, and induces neurodegeneration in rat cortical neurons. Our findings suggest that age-associated increase in serum tyrosine levels may effect neurocognitive and metabolic disorders and offer a plausible explanation for divergent results obtained in clinical trials using resveratrol." @default.
- W4281647810 created "2022-06-13" @default.
- W4281647810 creator A5002685947 @default.
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- W4281647810 date "2022-06-10" @default.
- W4281647810 modified "2023-10-18" @default.
- W4281647810 title "Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration" @default.
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- W4281647810 doi "https://doi.org/10.1038/s41467-022-30785-8" @default.
- W4281647810 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35688816" @default.
- W4281647810 hasPublicationYear "2022" @default.