M. Veliky, I. Shymanskyi, T. Kuchmerovska*, Yu. Parkhomenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine,
Department of Vitamins and Coenzymes, Kyiv;
*e-mail: tkuchmerovska@gmail.com

Received: 05 May 2025; Revised: 08 July 2025;
Accepted: 30 October 2025; Available on-line: 02 December 2025

Modern advances in molecular vitaminology are characterized by a marked expansion in understanding­ the molecular mechanisms underlying the actions of vitamins and their biologically active derivatives as highly effective compounds that ensure controlled interactions between cellular regulatory systems and metabolic processes. The molecular mechanisms of the pleiotropic effects of the hormonally active form of vitamin D₃, calcitriol (1α,25(OH)₂D₃), are realized in target tissues through vitamin D₃ receptors (VDR), which are present in virtually all cells. Our studies have focused on VDR-mediated effects, including modulation of the transcriptional activity of NF-κB, NFAT, HIF-1 and PPAR, as well as involvement of regulatory pathways such as HIF-1α/VEGF and RANK/NF-κB. We have also examined signaling through glucocorticoid and mine­ralocorticoid receptors, which play a key role in the antioxidant, anti-inflammatory, and anti-apoptotic effects of vitamin D₃ under normal conditions and in pathology (osteoporosis, neurodegenerative disorders associated with glucocorticoid-induced neurotoxicity and type 2 diabetes mellitus). The mechanisms of the neurotropic effects of vitamin B₃ (nicotinamide) and a derivative of nicotinic and amino butyric acid, nicotinoil-GABA (N-GABA), have also been studied. It has been demonstrated that nicotinamide (NAm) inhibits the development of diabetic neuropathy by reducing the activity and level of the PARP-1 enzyme, suppressing its fragmentation and preventing DNA damage in the brain tissue, and normalizing the nuclear levels of SIRT1 and SIRT2 proteins in neurons. One of the effective methodological approaches in our studies has been the investigation of thiamine-binding proteins in the brain and the effects of thiamine deficiency on the expression and state of neurospecific proteins. Based on our findings, we have formulated a working hypothesis regarding­ the molecular mechanisms of vitamin B1 involvement in the functioning of the cholinergic component of the nervous system. This hypothesis suggests that, in addition to the pool of thiamine diphosphate (ThDP) that binds to ThDP-dependent enzymes, nerve cells contain a rapidly exchangeable pool of thiamine derivatives that are involved in acetylcholine metabolism. The research achievements of our Department demonstrate the therapeutic potential of vitamins D₃, B₃, B₁, and their biologically active derivatives in preventing the develop­ment of neurodegenerative complications under various pathological conditions and provide a scientific basis for the development of novel vitamin supplements.