Reference : Thiamin derivatives in the brain of a mouse model of Alzheimer's disease and in cultured...
Scientific congresses and symposiums : Poster
Social & behavioral sciences, psychology : Neurosciences & behavior
http://hdl.handle.net/2268/129918
Thiamin derivatives in the brain of a mouse model of Alzheimer's disease and in cultured Neuroblastoma cells treated with benfotiamine
English
Vignisse, Julie mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique >]
Liégeois, Jean-François mailto [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique >]
Wins, Pierre []
Bettendorff, Lucien mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique >]
Jul-2011
No
International
FENS/IBRO Summer School 2011: Metabolic Aspects of Chronic Brain Diseases
du 20 au 26 juillet 2011
Gunzburg
Allemagne
[en] Alzheimer's disease ; Benfotiamine
[en] Alzheimer’s disease (AD) is a devastating neurodegenerative disorder for which any disease-modifying treatment is available. It is estimated that approximately 36 million people suffer from this disease and it comes with a high prize for the society. Recently, it has been shown that chronic administration of benfotiamine, a precursor of thiamin, in a mouse model of AD (APP/PS1 mice) significantly reduced key features of this disease namely memory impairment, β-amyloid accumulation and tau hyperphosphorylation. These beneficial effects are thought to be mediated by the PI3K/Akt/GSK3 signalling pathway (Pan et al., 2010). GSK3 is a kinase involved in the tau protein hyperphosphorylation in Alzheimer’s disease. It is however not clear how and which thiamine derivatives could interact with this kinase. Thiamine diphosphate is a well-known co-factor, in particular for mitochondrial pyruvate and oxo-glutarate dehydrogenases. However, other derivatives such as thiamine triphosphate and the newly discovered adenosine thiamine triphosphate are investigated in our laboratory. Therefore, we shall first try do determine whether benfotiamine (or one of its degradation products) or one of the above-mentioned thiamine derivatives are directly or indirectly involved in the regulation of the PI3K/Akt/GSK3 pathway in cultured neuroblastoma cells. For this purpose, neuroblastoma 2a cells will be grown in a thiamine-deficient medium containing benfotiamine, and thiamine derivatives (thiamine mono-, di- and triphosphate) will be measured by HPLC whereas Akt and GSK3 expression and phosphorylation levels will be assessed by immunoblotting. These experiments will give us new insights into the mechanism of action of thiamine derivatives, and according to the results obtained, we could then design new synthetic derivatives that would be more efficient than benfotiamine (very high doses were required in the animal experiments) in slowing down the neurodegenerative processes in Alzheimer’s disease.
http://hdl.handle.net/2268/129918

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