summary: Researchers have discovered a way to increase intracellular vitamin B6 levels and improve memory and learning by inhibiting the breakdown of vitamin B6. The study found that the natural substance 7,8-dihydroxyflavone inhibits the enzyme pyridoxal phosphatase, increasing vitamin B6 in nerve cells. This breakthrough discovery could lead to new treatments for psychiatric disorders and neurodegenerative diseases.
Key Facts:
- Vitamin B6 is linked to brain metabolism, memory, learning, and mental health.
- Researchers found that 7,8-dihydroxyflavone inhibits the enzyme that breaks down vitamin B6.
- The discovery could pave the way for new drug therapies for brain disorders.
sauce: University of Würzburg
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.
Publication E-Life
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 team published their findings in the journal Science. E-Life.
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 an effect could also be achieved by pharmacological agents, scientists are currently searching 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. The new findings regarding its effect as an inhibitor of pyridoxal phosphatase provide a new explanation for the efficacy of this substance.
This could improve understanding of the mechanisms behind psychiatric disorders and lead to new drug approaches to treat brain disorders, the scientists said in their research paper.
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.
About this Neuroscience Research News
author: Esther Knemeyer Pereira
sauce: University of Würzburg
contact: Esther Knemeyer-Pereira – University of Würzburg
image: Image courtesy of Neuroscience News
Original Research: Open access.
“7,8-Dihydroxyflavone is a direct inhibitor of human and mouse pyridoxal phosphatase” by Antje Gohla et al. E-Life
Abstract
7,8-Dihydroxyflavone is a direct inhibitor of human and mouse pyridoxal phosphatase.
Vitamin B6 deficiency has been linked to cognitive impairment in human brain diseases for decades, but the molecular mechanisms linking vitamin B6 to these pathologies remain poorly understood, and it is unclear whether vitamin B6 supplementation improves cognitive function.
Pyridoxal 5′-phosphate phosphatase (PDXP) is an enzyme that controls levels of pyridoxal 5′-phosphate (PLP), the coenzyme active form of vitamin B6, and may represent an entry point for alternative treatment of vitamin B6-related pathologies.
However, pharmacological PDXP inhibitors to test this concept are lacking. We have now identified PDXP and an age-dependent decline in PLP levels in the mouse hippocampus, providing a rationale for the development of PDXP inhibitors.
Combining small molecule screening, protein crystallography, and biolayer interferometry, we discovered, visualized, and analyzed 7,8-dihydroxyflavone (7,8-DHF) as a direct and potent PDXP inhibitor. 7,8-DHF binds and reversibly inhibits PDXP with low micromolar affinity and submicromolar potency. In mouse hippocampal neurons, 7,8-DHF increases PLP in a PDXP-dependent manner.
These findings demonstrate that PDXPs are a target for drug therapy. Of note, although 7,8-DHF is a well-studied molecule in brain injury models, its mechanism of action is actively debated.
The discovery of 7,8-DHF as a PDXP inhibitor brings new mechanistic insights into the controversy surrounding 7,8-DHF-mediated effects in the brain.
