A common vitamin has been given a lab-made boost, and researchers in Japan say it pushed immature brain cells to become neurons far better than the natural version.
Scientists at the Shibaura Institute of Technology created new vitamin K analogues aimed at making the compound more active in the nervous system. In cell tests, the strongest version was about three times more effective than natural vitamin K at inducing neural progenitor cells to turn into neurons.
The work, published online in ACS Chemical Neuroscience on July 03, 2025, was led by Associate Professor Yoshihisa Hirota and Professor Yoshitomo Suhara of the Department of Bioscience and Engineering.
Diseases including Alzheimer’s, Parkinson’s, and Huntington’s damage the brain by destroying neurons. Current medicines can ease some symptoms, and Alzheimer’s treatments such as lecanemab and donanemab can slow decline in some people with early disease, but they do not rebuild damaged brain tissue or restore lost memories.
Vitamin K is best known for blood clotting and bone health, but researchers have also linked it to brain protection and neuronal differentiation. One natural form, menaquinone 4, or MK-4, is active in the body, though the researchers said its effects may be too weak on their own for regenerative medicine.
To make it stronger, the team synthesized 12 hybrid vitamin K homologs. Some were linked to retinoic acid, an active metabolite of vitamin A known to promote neuronal differentiation. Others included a carboxylic acid moiety or a methyl ester side chain.
When the team tested the compounds in mouse neural progenitor cells, the hybrid molecules preserved the biological activity of both vitamin K and retinoic acid. The researchers also measured microtubule associated protein 2, or Map2, a marker associated with neuronal growth.
One compound stood out. It combined the retinoic acid structure with a methyl ester side chain and showed threefold higher neuronal differentiation activity than the control, along with stronger activity than natural vitamin K compounds. The researchers called it Novel VK.
Dr. Hirota said, “The newly synthesized vitamin K analogues demonstrated approximately threefold greater potency in inducing the differentiation of neural progenitor cells into neurons compared to natural vitamin K. Since neuronal loss is a hallmark of neurodegenerative diseases such as Alzheimer’s disease, these analogues may serve as regenerative agents that help replenish lost neurons and restore brain function.”
The team also looked at how vitamin K might be producing these effects. By comparing gene expression in neural stem cells treated with MK-4 against cells treated with a compound that suppresses neuronal differentiation, they identified metabotropic glutamate receptors, or mGluRs, as a possible driver of the process through downstream epigenetic and transcriptional regulation.
The effect of MK-4 was specifically tied to mGluR1. The source material said mGluR1 has already been linked to synaptic transmission, and mice lacking mGluR1 show motor and synaptic problems.
The researchers then used structural simulations and molecular docking studies to test how the compound might interact with mGluR1. Their results suggested that Novel VK had stronger binding affinity for mGluR1 than MK-4.
They also tested how well Novel VK entered cells and converted into bioactive MK-4. Inside cells, MK-4 levels rose in a concentration dependent way, and Novel VK converted into MK-4 more easily than natural vitamin K.
In mouse experiments, Novel VK showed a stable pharmacokinetic profile, crossed the blood brain barrier, and produced higher MK-4 concentrations in the brain than the control.
The findings are based on cell studies and mouse experiments, not human trials. The source material said no vitamin K derived drug has yet been shown to repair the brains of people with Alzheimer’s, Parkinson’s, or Huntington’s disease.
Dr. Hirota said, “Our research offers a potentially groundbreaking approach to treating neurodegenerative diseases. A vitamin K-derived drug that slows the progression of Alzheimer’s disease or improves its symptoms could not only improve the quality of life for patients and their families but also significantly reduce the growing societal burden of healthcare expenditures and long-term caregiving.”
Read more from Science Daily.
