Abstract
Thiamine (vitamin B1) is essential for brain function because of the coenzyme role of thiamine diphosphate (ThDP) in glucose and energy metabolism. In order to compensate thiamine deficiency, several thiamine precursors with higher bioavailability were developed since the 1950s. Among these, the thioester benfotiamine (BFT) has been extensively studied and has beneficial effects both in rodent models of neurodegeneration and in human clinical studies. BFT has antioxidant and anti-inflammatory properties that seem to be mediated by a mechanism independent of the coenzyme function of ThDP. BFT has no adverse effects and improves cognitive outcome in patients with mild Alzheimer’s disease (AD). Recent in vitro studies show that another thiamine thioester, dibenzoylthiamine (DBT) is even more efficient that BFT, especially with respect to its anti-inflammatory potency. Thiamine thioesters have pleiotropic properties linked to an increase in circulating thiamine concentrations and possibly in hitherto unidentified metabolites in particular open thiazole ring derivatives. The identification of the active neuroprotective derivatives and the clarification of their mechanism of action open extremely promising perspectives in the field of neurodegenerative, neurodevelopmental and psychiatric conditions.
Highlights
Thiamine, the first vitamin to be isolated [1], is an essential micronutrient for all animal species
We studied the metabolism of BFT in more detail in cultured neuroblastoma cells [33]
MRNA levels of GSK3β were increased in the modified swim test and when the mice were exposed to predator stress. This increase was fully reversed when the animals were treated with BFT (200 mg/kg per day). These findings suggest that the beneficial effects of BFT treatment in mouse models of brain disease may involve a decrease of GSK3β activity
Summary
Thiamine (vitamin B1), the first vitamin to be isolated [1], is an essential micronutrient for all animal species. As these enzymes catalyze essential steps in glucose oxidation, it is obvious that ThDP is an indispensable cofactor for energy metabolism (Figure 1) and it is not surprising that TD will have deleterious effects on organs that are dependent on oxidative metabolism such as the nervous system and the heart. In Wernicke–Korsakoff’s syndrome, irreversible lesions appear in the thalamus and mammillary bodies, while the cortex is largely spared These observations have led to the idea that thiamine (or a thiamine derivative other than ThDP) may exert neuromodulatory or neuroprotective actions through mechanisms unrelated to the coenzyme role of. We will highlight the neuroprotective effects of a hitherto unexplored thiamine precursor, O,S-dibenzoylthiamine (DBT) This compound has powerful antioxidant and anti-inflammatory properties similar to BFT but is active at substantially lower concentrations [29]. This is the case for the (Z)-isomer of BFT shown here and which is the only one that should be called “benfotiamine”
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