Vitamin B6 is important for brain metabolism. Consequently, in various mental illnesses, a low level of vitamin B6 is associated with problems with memory and learning ability, with a depressed mood and even with genuine depression. In older people, insufficient vitamin B6 is linked to memory loss and dementia.
Although some of these observations were made decades ago, the exact role of vitamin B6 in mental illness is still unclear. What is clear, however, is that increased intake of vitamin B6 alone, for example in the form of dietary supplements, is not sufficient to prevent or treat disorders of brain function.
Publication in eLife
A research team from the Medical University of Würzburg has now discovered another way to more effectively increase vitamin B6 levels in cells: by specifically inhibiting its intracellular degradation. Antje Gohla, Professor of Biochemical Pharmacology at the Department of Pharmacology and Toxicology at the Julius-Maximilians-Universität Würzburg (JMU), is responsible for this.
Other participants come from the Rudolf Virchow Center for Integrative and Translational Bioimaging at JMU, the Leibniz-Forschungsinstitut für Molekulare Pharmakologie-FMP Berlin and the Institute of Clinical Neurobiology at the University Hospital of Würzburg. The team has now published the results of their research in the scientific journal. eLife.
Enzyme blocking improves learning ability
“In previous studies we were already able to show that the genetic deactivation of the enzyme pyridoxal phosphatase, which degrades vitamin B6, in mice improves the spatial learning and memory capacity of the animals,” explains Antje Gohla. To investigate whether these effects can also be achieved with pharmacological agents, scientists have looked for substances that bind and inhibit pyridoxal phosphatase.
Successfully: “In our experiments we have identified a natural substance that can inhibit pyridoxal phosphatase and thus slow down the degradation of vitamin B6,” explains the pharmacologist. In fact, the working group managed to increase the levels of vitamin B6 in nerve cells that participate in learning and memory processes. The name of this natural substance: 7,8-Dihydroxyflavone.
New approach to drug therapy
7,8-Dihydroxyflavone has already been described in many other scientific articles as a molecule that can improve learning and memory processes in models of mental illness. New knowledge about its effect as a pyridoxal phosphatase inhibitor now opens up new explanations for the effectiveness of this substance. This could improve the mechanistic understanding of mental disorders and represent a new pharmacological approach to the treatment of brain disorders, the scientists write in their study.
The team also considers it a great success that 7,8-dihydroxyflavone was identified for the first time as a pyridoxal phosphatase inhibitor; After all, this class of enzymes is considered particularly challenging for drug development.
A long road to a drug
When will people benefit from this discovery? “It’s too early to say,” explains Marian Brenner, first author of the study. However, there is much evidence that it may be beneficial to use vitamin B6 in combination with pyridoxal phosphatase inhibitors for various mental disorders and neurodegenerative diseases.
In the next step, Gohla and his team want to develop improved substances that inhibit this enzyme precisely and very effectively. Such inhibitors could then be used to specifically test whether increasing cellular levels of vitamin B6 is useful in mental or neurodegenerative diseases.