"Supercharged" vitamin K derivatives offer new hope for neurodegenerative diseases
- Researchers synthesized a series of hybrid vitamin K analogues (linked with retinoic acid or modified side chains) that show about threefold greater potency in driving neural progenitor cells to differentiate into neurons compared to natural vitamin K (MK‑4).
- Mechanistic studies revealed that vitamin K activates mGluR1‑mediated signaling, triggering downstream epigenetic and transcriptional programs that steer stem cells toward a neuronal fate.
- Structural modeling and molecular docking showed that the lead analogue (Novel VK / compound 7) binds more strongly to mGluR1 than natural MK‑4, reinforcing the receptor's central role.
- In vivo testing in mice demonstrated favorable pharmacokinetics: the analogue penetrated the blood–brain barrier, reached higher brain levels of MK‑4 and was more efficiently converted intracellularly than native vitamin K.
- Together, the findings point to synthetic vitamin K derivatives as promising candidates for neuron regeneration therapies in neurodegenerative diseases — though further work is required on safety, efficacy in disease models and dosing before clinical use.
Researchers have engineered new analogues of vitamin K that may help regenerate neurons lost in disorders such as Alzheimer's, Parkinson's and Huntington's disease, offering a possible new direction in the search for therapies that go beyond symptom relief.
Neurodegenerative disorders arise when nerve cells (neurons) progressively deteriorate and die, leading to severe impairments in memory, cognition and motor function. While current medications can alleviate symptoms, they cannot halt or reverse the underlying cell loss — creating a pressing need for regenerative treatments that replace or repair damaged neurons.
In a new study published in ACS Chemical Neuroscience, scientists at Japan's Shibaura Institute of Technology, led by Associate Professor Yoshihisa Hirota and Professor Yoshitomo Suhara, report that they have synthesized a series of hybrid vitamin K molecules that show markedly enhanced ability to drive neuronal differentiation in lab experiments.
The team created twelve novel vitamin K derivatives by fusing vitamin K with retinoic acid (a metabolite of vitamin A known to promote neuron formation), or by modifying the side chains with carboxylic acid or methyl ester groups. When tested in mouse neural progenitor cells, one of these compounds—termed Novel VK in the paper—boosted neuronal differentiation nearly threefold compared to control, outperforming natural vitamin K forms such as menaquinone‑4 (MK‑4).
Mechanistic insights from the study suggest that the neurogenic effect of vitamin K is mediated via metabotropic glutamate receptor 1 (mGluR1).
Novel VK targets mGluR1 to drive epigenetic neuronal fate and reaches the brain with superior MK‑4 conversion
In transcriptomic analyses of neural stem cells treated with MK‑4 versus an inhibitory compound, the researchers found that vitamin K activates mGluR1-related signaling, which in turn drives downstream epigenetic changes and transcriptional reprogramming toward neuronal fate. Structural modeling and molecular docking further showed that Novel VK binds more strongly to mGluR1 than natural MK‑4, strengthening the case for this receptor as a key player in the process.
In vivo testing in mice revealed promising pharmacological properties: Novel VK demonstrated stable pharmacokinetics, efficient penetration across the blood‑brain barrier and higher accumulation of MK‑4 in brain tissue compared to controls. The authors also found that Novel VK is more readily metabolized to MK‑4 inside cells than native vitamin K, supporting its potential as a pro‑drug or precursor in neural tissues.
Taken together, the findings suggest that synthetic vitamin K derivatives may offer a novel, mechanism‑based strategy to stimulate neuron regeneration in degenerative brain diseases. As Dr. Hirota put it, "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."
However, the authors caution that much work remains before this approach can become clinically viable. Additional studies are needed to verify safety, efficacy in disease models, long‑term effects and dosing parameters. Nonetheless, the research marks an exciting step toward regenerative approaches in treating neurodegeneration — offering hope that the brain's own restorative potential might one day be harnessed to counteract diseases once considered inexorable.
According to
BrightU.AI's Enoch, vitamin K, particularly vitamin K2 (menaquinone), plays a crucial role in bone health by aiding calcium deposition in bones and preventing its accumulation in arteries. It also supports cardiovascular health by inhibiting arterial calcification and promoting cardiovascular health.
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