Novel Vitamin K Analogs Show Promise in Neurodegenerative Disease treatment
Researchers have developed novel vitamin K analogs withโ significantly enhanced neuroprotective and neuronal differentiation-inducing properties, offering a potential new avenue for treating neurodegenerative diseases like Alzheimer’s.The study, conducted at the Shibaura Institute ofโค Technology and published in ACS Chemical Neuroscience, โdetails the creation and testing of โhybrid compounds combiningโฃ structural elements of vitamin Kโข and retinoic acid.
Vitamin K and retinoic acid exert their biological effects by regulating transcriptional activity through the steroid and xenobiotic receptor (SXR) and retinoic acid receptor (RAR), respectively.The researchers synthesized hybridโ homologs of these compounds and found that โthey retained the biological activityโ of both parent molecules when tested on mouse neural progenitor cells. Specifically, โa compound incorporating both theโฃ conjugated โstructure of retinoic โขacid and a methyl ester side chain demonstrated a three-fold increase in neuronal differentiation activity compared toโ controls and outperformed natural vitamin K compounds – designated as a “Novel vitamin K analog” (Novel VK).Neuronal differentiation was quantified by measuring the expression of microtubule-associated โฃprotein 2 (Map2), โคa โkey marker of neuronal growth.
Toโฃ understand โ how โข vitamin K exerts its neuroprotectiveโ effects, the team compared โgene expression profiles of neural stem cells treated with MK-4, a known differentiation-inducing compound, to those treated โฃwith a differentiation-suppressing compound. This analysis revealed that metabotropic glutamate receptors (mGluRs) play a crucial role in mediating vitamin K-induced neuronal differentiation, operating through downstream epigenetic and transcriptional regulation. The effect was specifically linked to mGluR1, a โขreceptor previously associated with synaptic transmission and whose deficiency inโ mice leads โขto motor and synaptic dysfunction – hallmarks of neurodegenerative diseases.
Further inquiry using structural simulations and molecular docking studies confirmed a direct interaction between Novel VK and mGluR1, revealing a stronger binding affinity thanโ observed with natural vitamin K. Crucially, the researchers demonstrated that Novel VK is readily converted to the bioactive MK-4 both in vitro and in vivo. Cellular uptake studies showed a โฃconcentration-dependent increase in intracellular MK-4 levels, and mice treated with Novel VK โexhibited a more stable pharmacokinetic profile, efficient blood-brain barrier โpenetration, and higher brain concentrationsโ of MK-4 compared โขto controls.
these findings illuminate the mechanism behind vitamin K’s neuroprotective effects and suggest that structurally modified analogs like Novel VK can significantly enhance these benefits.As Dr. Hirota, the lead researcher, states, “Our research offers a potentially groundbreaking โapproach โto โขtreating neurodegenerative diseases. โฃA vitaminโ K-derived drug that slows the progression of Alzheimer’s disease or improves its โคsymptoms coudl notโค only โขimprove the qualityโฃ of life for patients and their families but also significantly reduce the growing societal burden of healthcare expendituresโฃ and long-term caregiving.” The study represents a promising step โtowards the โgrowth of novel therapeutic agents for neurological diseases,offering hope for improved treatments and a better future for patients and their families.
Source: Shibaura Institute of Technology. Hirota, Y., etโฃ al. (2025).โ A New Class of Vitamin K Analogues Containing the Side Chain of Retinoicโค Acid Have Enhanced Activity for Inducingโ Neuronal Differentiation. ACS Chemical Neuroscience. doi.org/10.1021/acschemneuro.5c00111.
