Low levels of vitamin B6 have a negative impact on brain performance, and now a team of researchers from the Medical School of the University of Würzburg has found a way to slow down the vitamin’s degradation.
Vitamin B6 is important for brain metabolism. Thus, in various psychiatric disorders, low vitamin B6 levels are associated with poor memory and learning ability, depressed mood, and even true depression. In older adults, vitamin B6 deficiency can lead to memory loss and dementia.
Although some of these observations were made decades ago, the exact role of vitamin B6 in psychiatric disorders remains largely unclear, but what is clear is that simply increasing your intake of vitamin B6, for example in the form of a supplement, is not enough to prevent or treat brain dysfunction.
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A research team from the Medical Faculty of the University of Würzburg has now found another way to increase intracellular vitamin B6 concentrations more effectively: by specifically inhibiting the breakdown of vitamin B6 within the cells. The study was led by Antje Gora, professor of biochemical pharmacology at the Department of Pharmacology and Toxicology at the Julius-Maximilians-University Würzburg (JMU).
Other participants come from JMU’s Rudolf Virchow Center for Integrative and Translational Bioimaging, the Leibniz Institute of Molecular Pharmacology (FMP) Berlin and the Institute of Clinical Neurobiology at the University Hospital Würzburg. The research team has now published their findings in the scientific journal eLife.
Enzyme inhibition improves learning ability
“Previous studies have already shown that genetically switching off the vitamin B6-degrading enzyme pyridoxal phosphatase in mice improves the animals’ spatial learning and memory abilities,” explains Antje Gora. To see whether such effects can also be achieved by pharmacological substances, the scientists are now looking for substances that bind to and inhibit pyridoxal phosphatase.
They succeeded. “In our experiments, we identified a natural substance that is able to inhibit pyridoxal phosphatase and slow down the breakdown of vitamin B6,” explains the pharmacologist. The research group was indeed able to increase vitamin B6 levels in nerve cells involved in learning and memory processes. The name of this natural substance is 7,8-dihydroxyflavone.
New approaches to drug therapy
7,8-Dihydroxyflavone has already been described in numerous other scientific papers as a molecule capable of improving learning and memory processes in disease models of psychiatric disorders. New knowledge about its effect as an inhibitor of pyridoxal phosphatase now allows a new explanation for the effectiveness of this substance. This could lead to a better understanding of the mechanisms of psychiatric disorders and a new pharmacological approach for the treatment of brain diseases, the scientists say in their study.
The team also considers it a major success that 7,8-dihydroxyflavone has been identified for the first time as an inhibitor of pyridoxal phosphatase, since, after all, this class of enzymes is considered particularly challenging for drug development.
The long road to drugs
When will this discovery benefit people? “It’s too early to tell,” explains Marianne Brenner, first author of the study. But there is growing evidence to suggest that using vitamin B6 in combination with pyridoxal phosphatase inhibitors could be beneficial for a range of psychiatric and neurodegenerative disorders.
As a next step, Gora and her team aim to develop improved substances that precisely and effectively inhibit this enzyme. Such inhibitors could be used to specifically test whether increasing intracellular levels of vitamin B6 could be effective in treating psychiatric and neurodegenerative disorders.
Publication
7,8-Dihydroxyflavone is a direct inhibitor of human and mouse pyridoxal phosphatase. Marian Brenner, Christoph Zink, Linda Witzinger, Angelika Keller, Kerstin Hadamek, Sebastian Bothe, Martin Neuenschwander, Carmen Villmann, Jens Peter von Kries, Hermann Schindelin, Elisabeth Jeanclos, and Antje Gohla. eLife,
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