H3K27 of Slc40a1 was methylated in senile mice, YP peptide can demethylate it to restore ferriportin to excrete brain iron, thus alleviating dementia

With aging, iron will accumulate in the brain, catalyzing oxidative radicals that damage brain neurons and induceAlzheimer's disease. In this experiment, we observed that in the brains of senile mice, the iron-exporting protein ferriportin was decreased. Further investigation indicated that H3K27 of the slc40a1 gene was methylated and that the methyltransferase Ezh2 was activated. To discharge the excessive iron in the brains of senile mice, we developed the YP peptide, and with it, we demethylated H3K27me of Slc40a1 by phosphorylation, activating the demethylase Kdm6a and inhibiting methyltransferase Ezh2. Consequently, the transcription of Slc40a1 was enhanced,and ferriportin was resumed. Thesenile brain reacquired the function of iron excretion, and as a result, the radicals in the brain weredecreased,and neuron damage was reduced, which finally restored the intelligence of dementia senile mice. Thus, YP could be a potential drug in the prevention of Alzheimer's disease