Physiological Improvement in Patients with Charcot-Marie-Tooth Disease by Pharmacological Doses of Thiamine Correlates with Increased Blood Levels of Thiamine Diphosphate DOI Open Access
Artem V. Artiukhov, Olga N. Solovjeva, Н. В. Балашова

et al.

Published: Nov. 10, 2023

Charcot-Marie-Tooth (CMT) neuropathy is a polygenic disorder of peripheral nerves with no effective cure. Thiamine (vitamin B1) neurotropic compound improving neuropathies. Our study shows therapeutic potential daily oral administration thiamine or its membrane-penetrating form sulbutiamine in CMT patients, by following their physiological performance along the blood levels coenzyme (thiamine diphosphate, ThDP), endogenous transketolase (TK) activity (holoTK), total TK (holoTK and apoTK) saturation ThDP (holoTK/(holoTK+apoTK)). The patients exhibit significant positive correlation hand grip strength. Both may decrease minor fraction apoenzyme, shifting activities to lower limit 0.03-0.04 U/mL. Although average ThDP, holoTK apoTK do not significantly differ between control groups, high interpersonal variations activation are inherent control, but CMT, subjects. difference associated statistically subjects only. Gender dependence negative correlations reversal vs. controls shown. Thus, benefits pharmacological doses linked changes thiamine-dependent metabolic network disease healthy state.

Language: Английский

Pharmacological Doses of Thiamine Benefit Patients with the Charcot–Marie–Tooth Neuropathy by Changing Thiamine Diphosphate Levels and Affecting Regulation of Thiamine-Dependent Enzymes DOI
Artem V. Artiukhov, Olga N. Solovjeva, Н. В. Балашова

et al.

Biochemistry (Moscow), Journal Year: 2024, Volume and Issue: 89(7), P. 1161 - 1182

Published: July 1, 2024

Language: Английский

Citations

5
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 DOI Open Access
Vasily A. Aleshin, А. В. Граф, Artem V. Artiukhov

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12405 - 12405

Published: Aug. 3, 2023

Epilepsy is characterized by recurrent seizures due to a perturbed balance between glutamate and GABA neurotransmission. Our goal reveal the molecular mechanisms of changes upon repeated challenges this balance, suggesting knowledge-based neuroprotection. To address goal, set metabolic indicators in post-seizure rat brain cortex compared before after pharmacological kindling with pentylenetetrazole (PTZ). Vitamins B1 B6 supporting energy neurotransmitter metabolism are studied as neuroprotectors. PTZ increases seizure severity (1.3 fold, p < 0.01), elevating rearings (1.5 = 0.03) steps out walls (2 0.01). In kindled vs. non-kindled rats, p53 level increased 1.3 fold (p 0.03), reciprocating 1.4-fold 0.02) decrease activity 2-oxoglutarate dehydrogenase complex (OGDHC) controlling degradation. Further, decreased expression deacylases SIRT3 (1.4 0.01) SIRT5 reciprocates acetylation 15 kDa proteins 1.5 Finally, abrogates stress response multiple saline injections control animals, manifested activities pyruvate complex, malic enzyme, glutamine synthetase malate activity. Post-seizure animals demonstrate correlations levels (r 0.79, 0.05). The duration 0.59, 0.05) 0.58, 0.02), respectively, substituted correlation latency OGDHC 0.69, vitamins administration, testifying vitamins-dependent impact on glutamate/GABA metabolism. also abrogate behavioral parameters 0.53–0.59, 0.03). Thus, modified behavior rats associated vitamin-dependent amino acids, linked key regulators: p53, OGDHC, SIRT5.

Language: Английский

Citations

9
Micronutrient Deficiency in Inherited Metabolic Disorders Requiring Diet Regimen: A Brief Critical Review DOI Open Access
Albina Tummolo,

Rosa Carella,

Donatella De Giovanni

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(23), P. 17024 - 17024

Published: Nov. 30, 2023

Many inherited metabolic disorders (IMDs), including of amino acid, fatty and carbohydrate metabolism, are treated with a dietary reduction or exclusion certain macronutrients, putting one at risk reduced intake micronutrients. In this review, we aim to provide available evidence on the most common micronutrient deficits related specific approaches management their deficiency, in meanwhile discussing main critical points each nutritional supplementation. The emerging concepts that great heterogeneity clinical practice exists, as well no univocal abnormalities. phenylketonuria, for example, micronutrients recommended be supplemented through protein substitutes; however, not all formulas equally some them added Data pyridoxine riboflavin status these patients particularly scarce. long-chain acid oxidation disorders, recommendations supplementation available. Regarding metabolism difficult-to-ascertain sugar content is still matter concern. A ketogenic diet may predispose both oligoelement overload, therefore deserves formulations. conclusion, our overview out lack unanimous deficiencies, need formulations IMDs, necessity high-quality studies, under-investigated deficits.

Language: Английский

Citations

5
A challenging interplay between basic research, technologies and medical education to provide therapies based on disease mechanisms DOI Creative Commons
Victoria I. Bunik

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Aug. 20, 2024

A challenging interplay between basic research, technologies and medical education to provide therapies based on disease mechanisms

Language: Английский

Citations

1
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 DOI Creative Commons

Mariana Martínez Barreiro,

Lucía Vázquez Alberdi,

Lucila De León

et al.

Biology, Journal Year: 2023, Volume and Issue: 12(10), P. 1324 - 1324

Published: Oct. 10, 2023

The main human hereditary peripheral neuropathy (Charcot-Marie-Tooth, CMT), manifests in progressive sensory and motor deficits. Mutations the compact myelin protein gene pmp22 cause more than 50% of all CMTs. CMT1E is a subtype CMT1 myelinopathy carrying micro-mutations pmp22. Trembler-J mice have spontaneous mutation identical to that present patients. PMP22 mainly (but not exclusively) expressed Schwann cells. Some studies found presence together with some anomalies CNS CMT Recently, we identified higher hippocampal expression elevated levels anxious behavior TrJ/+ compared those observed wt. In paper, delve deeper into central modeled analyzing vivo cerebrovascular component by Ultrafast Doppler, exploring vascular structure scanning laser confocal microscopy, behavioral profile anxiety difficulty tests. We hippocampi increased blood flow vessel volume wild type. Together this, an anxiety-like difficulties described earlier. demonstrate there are specific hemodynamics associated clinical phenotype, model disease.

Language: Английский

Citations

2
Pharmacological Doses of Thiamine Benefit Patients with Charcot–Marie–Tooth Neuropathy, Changing the Thiamine Diphosphate Levels and Dependent Enzyme Regulation DOI
Artem V. Artiukhov, Olga N. Solovjeva, Н. В. Балашова

et al.

Биохимия, Journal Year: 2024, Volume and Issue: 89(7), P. 1149 - 1173

Published: July 15, 2024

Charcot–Marie–Tooth (CMT) neuropathy is a polygenic disorder of peripheral nerves with no effective cure. Thiamine (vitamin B1) neurotropic compound improving neuropathies. Our pilot study characterizes therapeutic potential daily oral administration thiamine (100 mg) in CMT and its molecular mechanisms. The patient hand grip strength determined before after the along blood levels coenzyme form (thiamine diphosphate, ThDP), activities endogenous (without ThDP assay medium) holo-transketolase total (with transketolase, transketolase activation by [1-(holo-transketolase/total transketolase),%], corresponding to fraction ThDP-free apo-transketolase. Single cases sulbutiamine (200 or benfotiamine (150 reveal their effects on assayed parameters within those thiamine. Administration pharmacological forms increases patients. Comparison thiamin status patients varied disease that control subjects without diagnosed pathologies has not found significant differences average ThDP, distribution between holo apo forms. However, regulation thiamine/ThDP differs groups. In medium, does activate patients, while statistically group. supplementation vivo paradoxically decreases effect observed Correlation analysis reveals sex-specific relationships disease. Thus, our findings link physiological benefits changes status, characterized regulation.

Language: Английский

Citations

0
Physiological Improvement in Patients with Charcot-Marie-Tooth Disease by Pharmacological Doses of Thiamine Correlates with Increased Blood Levels of Thiamine Diphosphate DOI Open Access
Artem V. Artiukhov, Olga N. Solovjeva, Н. В. Балашова

et al.

Published: Nov. 10, 2023

Charcot-Marie-Tooth (CMT) neuropathy is a polygenic disorder of peripheral nerves with no effective cure. Thiamine (vitamin B1) neurotropic compound improving neuropathies. Our study shows therapeutic potential daily oral administration thiamine or its membrane-penetrating form sulbutiamine in CMT patients, by following their physiological performance along the blood levels coenzyme (thiamine diphosphate, ThDP), endogenous transketolase (TK) activity (holoTK), total TK (holoTK and apoTK) saturation ThDP (holoTK/(holoTK+apoTK)). The patients exhibit significant positive correlation hand grip strength. Both may decrease minor fraction apoenzyme, shifting activities to lower limit 0.03-0.04 U/mL. Although average ThDP, holoTK apoTK do not significantly differ between control groups, high interpersonal variations activation are inherent control, but CMT, subjects. difference associated statistically subjects only. Gender dependence negative correlations reversal vs. controls shown. Thus, benefits pharmacological doses linked changes thiamine-dependent metabolic network disease healthy state.

Language: Английский

Citations

1