Diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease slowly damage the brain by destroying neurons, the cells that carry messages through the nervous system. When these cells are lost, people can experience memory loss, cognitive decline, and movement difficulties, which are often severe enough to require ongoing care.
Current drugs can alleviate some symptoms, and recent Alzheimer’s treatments such as lecanemab and donanemab can slow decline in certain people with early-stage disease, but they do not restore lost memory or rebuild damaged brain tissue. That’s why researchers are pursuing another ambitious idea: helping the brain replace lost neurons.
Common vitamins for blood and bones
Vitamin K is best known for its role in blood clotting and bone health. But in recent years, scientists have also linked it to brain protection and neural differentiation, the process by which immature nerve cells become functioning neurons.
Menaquinone-4 (MK-4), a type of vitamin K, is naturally activated in the body. Still, its effects alone may not be powerful enough for future use in regenerative medicine targeting neurodegenerative diseases.
In a study published online in ACS Chemical Neuroscience on July 3, 2025, researchers at Japan’s Shibaura Institute of Technology created a vitamin K analog designed to be more active in the nervous system. The research was led by Associate Professor Yoshihisa Hirota and Professor Yoshitomo Suhara of the School of Life Science and Engineering.
Dr. Hirota explains, “Compared to natural vitamin K, newly synthesized vitamin K analogs showed approximately three times higher potency in inducing differentiation of neural progenitor cells into neurons. Since neuronal cell loss is a hallmark of neurodegenerative diseases such as Alzheimer’s disease, these analogs may act as regenerative agents that help replenish lost neurons and restore brain function.”
Building more powerful brain-active compounds
To make vitamin K more potent, the research team synthesized 12 hybrid vitamin K homologues. Some are associated with retinoic acid, an active metabolite of vitamin A known to promote neuronal differentiation. Others contained carboxylic acid moieties or methyl ester side chains. The researchers then compared how strongly these compounds promoted neural progenitor cells to become neurons.
Vitamin K and retinoic acid influence gene activity through various receptors. Vitamin K acts through the steroid and xenobiotic receptor (SXR), while retinoic acid acts through the retinoic acid receptor (RAR). When the researchers tested the compound on neural progenitor cells in mice, the hybrid molecule preserved the biological activity of both vitamin K and retinoic acid.
The researchers also measured microtubule-associated protein 2 (Map2), a marker associated with neuronal growth. One compound stood out. It combines a retinoic acid structure with a methyl ester side chain and exhibited 3-fold higher neurodifferentiation activity than controls and significantly stronger activity than natural vitamin K compounds. The researchers called it a novel vitamin K analogue (novel VK).
Amazing signals in the brain
The research team then investigated how vitamin K produces these neuroprotective effects. They compared gene expression in neural stem cells treated with MK-4, which promotes neural differentiation, and compounds that inhibit that process.
This analysis pointed to metabotropic glutamate receptors (mGluRs) that may help promote vitamin K-induced neuronal differentiation through downstream epigenetic and transcriptional regulation. The effects of MK-4 were specifically linked to mGluR1.
This connection is important because mGluR1 is already associated with synaptic transmission, or communication between neurons. Mice lacking mGluR1 exhibit motor and synaptic problems, features that overlap with the types of dysfunction seen in neurodegenerative diseases.
crossing into the brain
To investigate whether vitamin K compounds can interact with mGluR1, the researchers used structural simulations and molecular docking studies. 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 was converted into bioactive MK-4. Intracellularly, MK-4 levels increased in a concentration-dependent manner. Novel VK is also more easily converted to MK-4 than natural vitamin K.
Mouse experiments added another important finding. The novel VK exhibited a stable pharmacokinetic profile, crossed the blood-brain barrier, and produced higher MK-4 concentrations than controls in the brain.
Why the findings matter
This study highlights a potential path to treatments that go beyond symptom management. Vitamin K-based compounds may one day contribute to strategies aimed at slowing, delaying, and potentially reversing some of the neurodegeneration by encouraging neural progenitor cells to become neurons.
That remains a long-term goal. This discovery is based on cell studies and mouse experiments, not human trials. Vitamin K-derived drugs have not yet been proven to repair the brains of patients with Alzheimer’s, Parkinson’s, and Huntington’s diseases. Still, the results gave researchers clearer targets to develop future brain repair therapies, particularly the mGluR1 pathway.
The broader field of Alzheimer’s disease has already moved beyond purely symptom-based treatments. Although FDA-approved anti-amyloid therapies currently target the disease biology of early Alzheimer’s disease, they are not a cure and do not restore lost memory or cognitive function. If the regenerative approach ultimately proves safe and effective, it could lead to another challenge: replacing or restoring damaged nerve cells.
Dr. Hirota said, “Our research may provide an innovative approach to the treatment of neurodegenerative diseases. Vitamin K-derived drugs that slow the progression or improve symptoms of Alzheimer’s disease could not only improve the quality of life of patients and their families, but also significantly reduce the increasing medical costs and social burden of long-term care.”
It is hoped that this field of research will eventually move from promising experimental results to clinically meaningful treatments for people with neurological diseases.
About Associate Professor Yoshihisa Hirota of SIT
Dr. Yoshihisa Hirota is an associate professor in the Department of Life Science and Engineering, Faculty of Systems Science and Engineering, Shibaura Institute of Technology. He has also worked internationally as a visiting scholar at the University of Cincinnati.
His research focuses on medical science and nutritional biochemistry, with a particular focus on how fat-soluble vitamins and nucleic acids function in biological systems. Dr. Hirota has published 56 papers, and his research combines molecular biology and nutrition in the pursuit of better medical solutions and a longer healthy lifespan.
About Professor Yoshitomo Suhara of SIT
Dr. Yoshitomo Suhara is a professor in the Department of Life Science and Engineering, Faculty of Systems Science and Engineering, Shibaura Institute of Technology.
His research focuses on medicinal chemistry and drug discovery, particularly the creation of bioactive small molecules derived from fat-soluble vitamins such as vitamins D and K. He has authored over 100 peer-reviewed publications and several patent applications. His interdisciplinary projects include neurogenic compounds that promote neural differentiation, antiviral agents, and novel anticancer molecules.
Funding information
This research was supported in part by research grants from the Mishima Kaiun Memorial Foundation, the Suzuken Memorial Foundation, the Kose Beauty Research Foundation, the Koyanagi Foundation, the Toyo Food Technology University, the Scientific Research Promotion Fund, and the Takahashi Industrial and Economic Research Foundation.
Additional support comes from the International Collaborative Research Promotion Fund (Grant No. 18KK0455), Grants-in-Aid for Scientific Research (C) (Grant No. 20K05754, 18K11056, 21K11709, 24K14656), and the Young Researchers Development Support Project (Grant No. 18KK0455). 23K14091) From the Japan Society for the Promotion of Science (JSPS).
