Abstract |
The methionine cycle becomes disrupted in diseases such as Multiple Sclerosis and Alzheimer’s due to increased reactive nitrogen species which block methionine synthase (MTR). In a defective methionine metabolism cycle, there is a decrease in methyl donors such as betaine and SAM which is linked to a decrease in H3K4me3 and mitochondrial gene expression. To counteract the defective methionine cycle, neuroblastoma cells (SH-SY5Y) were first treated with homocysteine to replicate neurodegenerative conditions and study the efficacy of betaine supplementation. Betaine homocysteine methyltransferase (BHMT) has previously only been known to be found in the cytoplasm of the liver and kidney cells, however our data has shown that BHMT is present in the nucleus of neurons where it interacts with chromatin which allows the conversion of homocysteine to methionine in the nucleus. The pathway mediated by BHMT is induced by betaine and inhibited by SAH, thus decreasing betaine concentration under inflammatory conditions. After treating cell cultures with betaine, it was discovered that H3K4me3 concentration increases, thereby increasing mitochondrial gene expression. By performing western blots, we found BHMT regulates genes in the nucleus. These data suggests that supplementing neuronal cells with betaine will serve as a neuroprotective therapy for neurodegenerative diseases. Looking in cell cultures provides an insight into the mechanisms and therapeutic targets that can rebalance the methionine cycle and help to develop potential neuroprotective therapies.
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Modified Abstract |
The methionine cycle becomes disrupted in diseases such as Multiple Sclerosis and Alzheimer’s due to increased reactive nitrogen species which block methionine synthase (MTR). In a defective methionine metabolism cycle, there is a decrease in methyl donors such as betaine and SAM which is linked to a decrease in H3K4me3 and mitochondrial gene expression. Our data in neuronal cell culture suggests that supplementing neuronal cells with betaine will serve as a neuroprotective therapy for neurodegenerative diseases. Looking in cell cultures provides an insight into the mechanisms and therapeutic targets that can rebalance the methionine cycle and help to develop potential neuroprotective therapies.
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