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Synthetic Thioesters of Thiamine: Promising Tools for Slowing Progression of Neurodegenerative Diseases

EVENT: 
Weekly Seminar | Not Open to the Public
Who Should Attend: 
Researchers

Abstract

Thiamine (vitamin B1) is essential for brain. This is attributed to the coenzyme role of thiamine diphosphate (ThDP) in glucose and energy metabolism. However, thiamine triphosphorylated derivatives thiamine triphosphate and adenosine thiamine triphosphate —  the latter discovered in our laboratory — have been described, but heir physiological roles remain unknown. We have recently become interested in thiamine precursors with higher bioavailability. 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 no known adverse effects and improves cognitive outcome in patients with mild Alzheimer’s disease (AD). The mechanisms of action of BFT remains unknown. Indeed, in cell culture and animal models, BFT has antioxidant and anti-inflammatory properties that seem to be mediated by a mechanism independent of the coenzyme function of ThDP. 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 and is effective at lower concentrations. Thiamine thioesters have pleiotropic properties linked to an increase in circulating thiamine concentrations and possibly in hitherto unidentified 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.

Dr. Lucien Bettendorff's Figure

Publications

Julie Vignisse, Margaux Sambon, Anna Gorlova, Dmitrii Pavlov, Nicolas Caron, Brigitte Malgrange, Elena Shevtsova, Andrey Svistunov, Daniel C Anthony, Natalyia Markova, Natalyia Bazhenova, Bernard Coumans, Bernard Lakaye, Pierre Wins, Tatyana Strekalova, Lucien Bettendorff
Thiamine and benfotiamine prevent stress-induced suppression of hippocampal neurogenesis in mice exposed to predation without affecting brain thiamine diphosphate levels
Mol Cell Neurosci. 2017 Jul;82:126-136. doi: 10.1016/j.mcn.2017.05.005. Epub 2017 May 12.
Margaux Sambon, Aurore Napp, Alice Demelenne, Julie Vignisse, Pierre Wins, Marianne Fillet, Lucien Bettendorff
Thiamine and benfotiamine protect neuroblastoma cells against paraquat and β-amyloid toxicity by a coenzyme-independent mechanism
Heliyon. 2019 May 14;5(5):e01710. doi: 10.1016/j.heliyon.2019.e01710. eCollection 2019 May.
Margaux Sambon, Anna Gorlova, Alice Demelenne, Judit Alhama-Riba, Bernard Coumans, Bernard Lakaye, Pierre Wins, Marianne Fillet, Daniel C Anthony, Tatyana Strekalova, Lucien Bettendorff
Dibenzoylthiamine Has Powerful Antioxidant and Anti-Inflammatory Properties in Cultured Cells and in Mouse Models of Stress and Neurodegeneration
Biomedicines. 2020 Sep 18;8(9):361. doi: 10.3390/biomedicines8090361.

When

Tuesday, November 1, 2022 - 12:30pm

Where

Conference Room: 
Billings Building – Rosedale & Zoom

More Information

Darlene White

Conditions & Recovery

Neurodegenerative Diseases icon
Worldwide, 50 million people are living with Alzheimer's and other dementias.