The Therapeutic Potential of Vitamins B1, B3 and B6 in Charcot–Marie–Tooth Disease with the Compromised Status of Vitamin-Dependent Processes

Abstract

Understanding the molecular mechanisms of neurological disorders is necessary for the development of personalized medicine. When the diagnosis considers not only the disease symptoms, but also their molecular basis, treatments tailored to individual patients may be suggested. Vitamin-responsive neurological disorders are induced by deficiencies in vitamin-dependent processes. These deficiencies may occur due to genetic impairments of proteins whose functions are involved with the vitamins. This review considers the enzymes encoded by the DHTKD1, PDK3 and PDXK genes, whose mutations are observed in patients with Charcot–Marie–Tooth (CMT) disease. The enzymes bind or produce the coenzyme forms of vitamins B1 (thiamine diphosphate, ThDP) and B6 (pyridoxal-5′-phosphate, PLP). Alleviation of such disorders through administration of the lacking vitamin or its derivative calls for a better introduction of mechanistic knowledge to medical diagnostics and therapies. Recent data on lower levels of the vitamin B3 derivative, NAD+, in the blood of patients with CMT disease vs. control subjects are also considered in view of the NAD-dependent mechanisms of pathological axonal degeneration, suggesting the therapeutic potential of vitamin B3 in these patients. Thus, improved diagnostics of the underlying causes of CMT disease may allow patients with vitamin-responsive disease forms to benefit from the administration of the vitamins B1, B3, B6, their natural derivatives, or their pharmacological forms.

Pentylenetetrazole-Induced Seizures Are Increased after Kindling, Exhibiting Vitamin-Responsive Correlations to the Post-Seizures Behavior, Amino Acids Metabolism and Key Metabolic Regulators in the Rat Brain

“…According to the formula recommended by the US Food and Drug Administration (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInform ation/Guidances/ucm078932.pdf (accessed on 5 May 2023), the doses of vitamins B1 and B6 used in this study on rats (100 mg/kg each of the vitamins per day) correspond to a dose of 16 mg/kg, or 1 g for an average weight of 60 kg, in humans. These doses are within the interval of the doses used in the vitamin therapy [46,48,[97][98][99].…”

“…The acylations of the brain proteins is also detected along with the protein expression of the corresponding deacylases SIRT3 and SIRT5. In view of the critical dependence of the brain energy and neurotransmitters metabolism on vitamins B1 and B6, both exhibiting neurotropic action underlying potential therapeutic significance in neurological disorders including epilepsy [46][47][48], we also evaluate the metabolic and physiological effects of supplementation of vitamins B1 and B6 on the seizures without or after the PTZ kindling.…”

Micronutrient Deficiency in Inherited Metabolic Disorders Requiring Diet Regimen: A Brief Critical Review

“…Many vitamins (especially those of group B) regulate hundreds of metabolic reactions by acting as coenzymes, contributing to energy-producing reactions and facilitating metabolic and physiological processes throughout the body [9,[36][37][38][39].…”

In Vivo Ultrafast Doppler Imaging Combined with Confocal Microscopy and Behavioral Approaches to Gain Insight into the Central Expression of Peripheral Neuropathy in Trembler-J Mice

“…The diversity of genes and mutations causing CMT conditions produces phenotypes of varying severity, both in the onset and progression of the disease. There are no specific therapies for any form of CMT, the attenuation of clinical symptomatology being the most common application (i.e., vitamin supplements, pes cavus surgery) [49,50]. However, at present, although still in the testing stages in animal models, advances in virus-mediated gene therapies, the identification of sensitive molecular targets, and various pharmacological approaches aimed at improving clearance of protein aggresomes seem to be in the direction of a personalized medicine of the CMTs [51,52].…”