References of "Bettendorff, Lucien"
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See detailMyoferlin controls mitochondrial structure in pancreatic ductal adenocarcinoma, and affects tumor aggressiveness
Rademaker, Gilles ULiege; Hennequière, Vincent ULiege; Brohée, Laura ULiege et al

Poster (2017, September 22)

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, and the third leading cause of cancer related death. Therapeutic options remain very limited and are still based on ... [more ▼]

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, and the third leading cause of cancer related death. Therapeutic options remain very limited and are still based on classical chemotherapies. Cell fraction can survive to the chemotherapy and is responsible for tumor relapse. It appears that these cells rely on OXPHOS for survival. Myoferlin, a membrane protein involved in cell fusion was recently shown by our laboratory to be overexpressed in pancreatic cancer. In the present study, we discovered that myoferlin was more expressed in cell lines undergoing oxidative phosphorylation (OXPHOS) than in glycolytic cell lines. In the former cell lines, we showed that myoferlin silencing reduced OXPHOS activity and forced cells to switch to glycolysis. The decrease in OXPHOS activity is associated with mitochondrial network disorganization. Dynamin-related protein (DRP)-1 phosphorylation led us to suggest mitochondrial fission, reducing cell proliferation, ATP production and inducing autophagy and ROS accumulation. To confirm the clinical importance of myoferlin in PDAC, we showed that low myoferlin expression was significantly correlated to high overall survival. Myoferlin staining of PDAC sections was negatively correlated with several 18FDG PET indices indicating that glycolytic lesions had less myoferlin. As the mitochondrial function is demonstrated to enhance the cell resistance to the treatment, the metabolic switch forced by myoferlin silencing could open up a new perspective in the development of therapeutic strategies. [less ▲]

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See detailMetabolic inhibitors accentuate the anti-tumoral effect of HDAC5 inhibition
Hendrick, Elodie ULiege; Peixoto, Paul; Blomme, Arnaud et al

in Oncogene (2017)

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See detailElucidating the functions of brain GSK3α: possible synergy with GSK3β upregulation and reversal by antidepressant treatment in a mouse model of depressive-like behaviour
Pavlov, Dmitrii; Markova, Nataliia; Bettendorff, Lucien ULiege et al

in Behavioural Brain Research (2017), 335

positively correlated with floating behavior on the third test. A twoweek- long pretreatment regime with imipramine (7.5 mg/kg/day) or thiamine (200 mg/kg/day), which is known to have antidepressant ... [more ▼]

positively correlated with floating behavior on the third test. A twoweek- long pretreatment regime with imipramine (7.5 mg/kg/day) or thiamine (200 mg/kg/day), which is known to have antidepressant properties, reduced the GSK3β over-expression and decreased floating behavior on Day 5. GSK3α mRNA levels were measured in the hippocampus and prefrontal cortex on Days 1, 2 and 5. GSK3α expression was decreased in the prefrontal cortex on Day 2 and increased on Day 5. In this model, GSK3α mRNA changes were prevented by imipramine or thiamine treatment. There was a significant correlation between the expression of the two isoforms in the prefrontal cortex on Day 2 in untreated group. These results provide the first evidence for the potential involvement of GSK3α in depressive-like behaviours and as a target of anti-depressant therapy. Furthermore, the correlations suggest some cross-talk may exist between the two GSK3 isoforms. [less ▲]

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See detailThiamine and lipophilic thiamine precursors protect against oxidative damage in cultured neuroblastoma cells
Sambon, Margaux ULiege; Wins, Pierre; Bettendorff, Lucien ULiege

Conference (2017)

Recent evidence suggests that thiamine (vitamin B1) and some of its derivatives can exert prominent neuroprotective effects in the mammalian brain, particularly in mouse models of Alzheimer’s disease and ... [more ▼]

Recent evidence suggests that thiamine (vitamin B1) and some of its derivatives can exert prominent neuroprotective effects in the mammalian brain, particularly in mouse models of Alzheimer’s disease and tauopathies. As orally administered thiamine crosses intestinal and blood-brain barriers only slowly, precursors with higher bioavailability e.g. sulbutiamine, benfotiamine and dibenzoylthiamine, have been developed. We investigated the protective effects of thiamine and those precursors in neuroblastoma cells cultured in a medium containing minimal amounts of thiamine (10 nM). We induced oxidative stress by incubating the cells (24h) in the presence of the neurotoxic agent paraquat (0.25 mM). This treatment reduced cell viability by 40%. When thiamine or the precursors were present simultaneously, we observed protective effects by the precursors while free thiamine was ineffective.Dibenzoylthiamine was most efficient, affording complete protection of cells at 10-20 μM. It also caused the highest increase in intracellular thiamine, suggesting that the protection from oxidative damage is linked to increased levels of free thiamine (rather than thiamine diphosphate) in the neuroblastoma cells. These results and others from our laboratory raise the possibility that dibenzoylthiamine might useful as a neuroprotective agent in neurodegenerative disease. [less ▲]

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See detailThiamine and benfotiamine prevent stress-induced suppression of hippocampal neurogenesis in mice exposed to predation without affecting brain thiamine diphosphate levels
Vignisse, Julie ULiege; Sambon, Margaux ULiege; Gorlova, Anna et al

in Molecular and Cellular Neuroscience (2017), 82

Thiamine is essential for normal brain function and its deficiency causes metabolic impairment, specific lesions, oxidative damage and reduced adult hippocampal neurogenesis (AHN). Thiamine precursors ... [more ▼]

Thiamine is essential for normal brain function and its deficiency causes metabolic impairment, specific lesions, oxidative damage and reduced adult hippocampal neurogenesis (AHN). Thiamine precursors with increased bioavailability, especially benfotiamine, exert neuroprotective effects not only for thiamine deficiency (TD), but also in mouse models of neurodegeneration. As it is known that AHN is impaired by stress in rodents, we exposed C57BL6/J mice to predator stress for 5 consecutive nights and studied the proliferation (number of Ki67-positive cells) and survival (number of BrdU-positive cells) of newborn immature neurons in the subgranular zone of the dentate gyrus. In stressed mice, the number of Ki67- and BrdU-positive cells was reduced compared to non-stressed animals. This reduction was prevented when the mice were treated (200 mg/kg/day in drinking water for 20 days) with thiamine or benfotiamine, that were recently found to prevent stress-induced behavioral changes and glycogen synthase kinase-3β (GSK-3β) upregulation in the CNS. Moreover, we show that thiamine and benfotiamine counteract stress-induced bodyweight loss and suppress stress-induced anxiety-like behavior. Both treatments induced a modest increase in the brain content of free thiamine while the level of thiamine diphosphate (ThDP) remained unchanged, suggesting that the beneficial effects observed are not linked to the role of this coenzyme in energy metabolism. Predator stress increased hippocampal protein carbonylation, an indicator of oxidative stress. This effect was antagonized by both thiamine and benfotiamine. Moreover, using cultured mouse neuroblastoma cells, we show that in particular benfotiamine protects against paraquat-induced oxidative stress. We therefore hypothesize that thiamine compounds may act by boosting anti-oxidant cellular defenses, by a mechanism that still remains to be unveiled. Our study demonstrates, for the first time, that thiamine and benfotiamine prevent stress-induced inhibition of hippocampal neurogenesis and accompanying physiological changes. The present data suggest that thiamine precursors with high bioavailability might be useful as a complementary therapy in several neuropsychiatric disorders. [less ▲]

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See detailThiamine: Biological forms and function
Bettendorff, Lucien ULiege

Conference (2017)

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See detailThiamine and benfotiamine improve cognition and ameliorate GSK-3β-associated stressinduced behaviours in mice
Markova, Nataliia; Bazhenova, Nataliya; Anthony, Daniel C et al

in Progress in Neuro-Psychopharmacology & Biological Psychiatry (2017), 75

Thiamine deficiency in the brain has been implicated in the development of dementia and symptoms of depression. Indirect evidence suggests that thiamine may contribute to these pathologies by controlling ... [more ▼]

Thiamine deficiency in the brain has been implicated in the development of dementia and symptoms of depression. Indirect evidence suggests that thiamine may contribute to these pathologies by controlling the activities of glycogen synthase kinase (GSK)-3β. While decreased GSK- 3β activity appears to impair memory, increased GSK-3β activity is associated with the distressed/depressed state. However, direct evidence for the effects of thiamine on GSK-3β function were not have not been reported. Here, we administered thiamine or, the more bioavailable precursor, benfotiamine at 200 mg/kg/day for 2 weeks to C57BL/6J mice, to determine whether treatment might affect behaviours that are known to be sensitive to GSK-3β activity and whether such administration impacts on GSK-3β expression within the brain. The mice were tested in models of contextual conditioning and extinction, a 5-day rat exposure stress test, and a modified swim test with repeated testing. Imipramine (7.5 mg/kg/day) was administered as a positive control for thiamine or benfotiamine. As for imipramine, both compounds inhibited the upregulation of GSK-3β induced by predator stress or repeated swimming, and reduced floating scores and the predator stress-induced behavioural changes in anxiety and exploration. Coincident, thiamine and benfotiamine improved learning and extinction of contextual fear, and the acquisition of the step-down avoidance task. Together, our data indicate that thiamine and benfotiamine have antidepressant/anti-stress effects in naïve animals that are associated with reduced GSK-3β expression. Importantly, the treatment also had pro-cognitive actions despite the impact on GSK-3β activity. [less ▲]

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See detailInhibition of mitochondrial 2-oxoglutarate dehydrogenase impairs viability of cancer cells in a cell-specific metabolismdependent manner
Bunik, Victoria; Mkrtchyan, Garait; Grabarska, Aneta et al

in Oncotarget (2016), 7(26400), 26421

2-Oxoglutarate dehydrogenase (OGDH) of the tricarboxylic acid (TCA) cycle is often implied to be inactive in cancer, but this was not experimentally tested. We addressed the question through specific ... [more ▼]

2-Oxoglutarate dehydrogenase (OGDH) of the tricarboxylic acid (TCA) cycle is often implied to be inactive in cancer, but this was not experimentally tested. We addressed the question through specific inhibition of OGDH by succinyl phosphonate (SP). SP action on different cancer cells was investigated using indicators of cellular viability and reactive oxygen species (ROS), metabolic profiling and transcriptomics. Relative sensitivity of various cancer cells to SP changed with increasing SP exposure and could differ in the ATP- and NAD(P)H-based assays. Glioblastoma responses to SP revealed metabolic sub-types increasing or decreasing cellular ATP/NAD(P)H ratio under OGDH inhibition. Cancer cell homeostasis was perturbed also when viability indicators were SPresistant, e.g. in U87 and N2A cells. The transcriptomics database analysis showed that the SP-sensitive cells, such as A549 and T98G, exhibit the lowest expression of OGDH compared to other TCA cycle enzymes, associated with higher expression of affiliated pathways utilizing 2-oxoglutarate. Metabolic profiling confirmed the dependence of cellular SP reactivity on cell-specific expression of the pathways. Thus, oxidative decarboxylation of 2-oxoglutarate is significant for the interdependent homeostasis of NAD(P)H, ATP, ROS and key metabolites in various cancer cells. Assessment of cellspecific responses to OGDH inhibition is of diagnostic value for anticancer strategies. [less ▲]

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See detailCellular thiamine status is coupled to function of mitochondrial 2-oxoglutarate dehydrogenase
Mkrtchyan, Garik; Graf, Anastasia; Bettendorff, Lucien ULiege et al

in Neurochemistry International (2016), 101

Decreased thiamine and reduced activity of thiamine diphosphate (ThDP)-dependent 2-oxoglutarate dehydrogenase (OGDH) cause neurodegeneration. We hypothesized on concerted cell-specific regulation of the ... [more ▼]

Decreased thiamine and reduced activity of thiamine diphosphate (ThDP)-dependent 2-oxoglutarate dehydrogenase (OGDH) cause neurodegeneration. We hypothesized on concerted cell-specific regulation of the thiamine metabolism and ThDP-dependent reactions. We identified a smaller thiamine pool, a lower expression of the mitochondrial ThDP transporter, and a higher expression of OGDH in rat astrocytes versus neuroblastoma N2A. According to the data, the astrocytic OGDH may be up-regulated by an increase in intracellular ThDP, while the neuroblastomal OGDH functions at full ThDP saturation. Indeed, in rat astrocytes and brain cortex, OGDH inhibition by succinyl phosphonate (SP) enlarged the pool of thiamine compounds. Increased ThDP level in response to the OGDH inhibition presumably up-regulated the enzyme to compensate for a decrease in reducing power which occurred in SP-treated astrocytes. Under the same SP treatment of N2A cells, their thiamine pool and reducing power were unchanged, although SP action was evident from accumulation of glutamate. The presented data indicate that functional interplay between OGDH, other proteins of the tricarbocylic acid cycle and proteins of thiamine metabolism is an important determinant of physiology-specific networks and their homeostatic mechanisms. [less ▲]

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See detailMolecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical, structural and pathway analysis.
Mkrtchyan, Garik; Aleshin, Vasily; Parkhomenko, Yulia et al

in Scientific Reports (2015), 5

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See detailIn search of a physiological role for thiamine triphosphate and the 25-kDa thiamine triphosphatase
Bettendorff, Lucien ULiege; Lakaye, Bernard ULiege; Kohn, Grégory ULiege et al

Conference (2014, May 25)

In search of a physiological role for thiamine triphosphate and the 25-kDa thiamine triphosphatase L. BETTENDORFF, B. LAKAYE, G. KOHN AND P. WINS GIGA-Neurosciences, University of Liège, 4000-Liège ... [more ▼]

In search of a physiological role for thiamine triphosphate and the 25-kDa thiamine triphosphatase L. BETTENDORFF, B. LAKAYE, G. KOHN AND P. WINS GIGA-Neurosciences, University of Liège, 4000-Liège, Belgium Thiamine triphosphate (ThTP) was discovered over 60 years ago. Although it is present in most organisms from bacteria to mammals, its possible biological functions remain unclear. In contrast to thiamine diphosphate (ThDP), it is not a coenzyme. In E. coli cells, ThTP is transiently produced in response to amino acid starvation, while in mammalian cells, it is constitutively produced at a low rate. In some animal tissues, ThTP was able to phosphorylate proteins and activate a high-conductance anion channel in vitro. These observations raised the possibility of ThTP being part of a still uncharacterized cellular signaling pathway. Though it was long thought that ThTP is synthesized by a specific ThDP:ATP phosphotransferase, more recent studies indicate that two main mechanisms are involved: (1) in the cytosol adenylate kinase 1 can catalyze ThTP production from ThDP and ADP and (2) in brain mitochondria FoF1-ATP synthase can catalyze ThTP production from ThDP + Pi. The latter reaction is energized by the respiratory chain through a chemiosmotic mechanism analogous to oxidative phosphorylation. Both mechanisms are conserved from bacteria to mammals. While ThTP synthesis does not seem to require a specific enzyme, its hydrolysis in mammalian tissues is catalyzed by a very specific cytosolic 25 kDa thiamine triphosphatase (ThTPase). Because of this activity, steady-state ThTP levels are kept low in mammalian cells. ThTPase belongs to the CYTH superfamily of proteins which has representatives in all superkingdoms of life acting on tripolyphosphate and various triphosphorylated substrates. Although the whole chromosome region containing the ThTPase gene was lost in birds, orthologs of the ThTPase gene were found in all other known metazoan genomes. It seems that ThTPase activity appeared as a secondary acquisition of the CYTH proteins in the lineage leading from cnidarians to vertebrates. In particular, the Trp-53 residue of mammalian ThTPases plays a key role in substrate recognition and specificity by interacting with the thiazole part of ThTP. This residue is conserved in metazoan CYTH proteins with ThTPase activity. In order to gain insight into the physiological function(s) of the ThTP-ThTPase couple, we tried to produce a mouse invalidated in 25-kDa ThTPase. Surprisingly, we were unable to obtain any knockout animal, apparently because ThTPase seems to be required for spermatogenesis. As we previously showed that the enzyme is much more abundant in differentiated versus undifferentiated cells, we suspect that 25-kDa ThTPase might play a more general and important role during cell differentiation. Acknowledgments This work was supported by the F.R.S.-FNRS. LB and BL are respectively Research Director and Research Associate at the F.R.S.-FNRS. [less ▲]

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See detailBenfotiamine increases cell proliferation in adult mouse hippocampus
Vignisse, Julie ULiege; Caron, Nicolas; Malgrange, Brigitte ULiege et al

Poster (2014, May)

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See detail25KDa-Thiamine triphosphatase is essential for spermatozoid development in mice
Kohn, Grégory ULiege; Ectors, Fabien ULiege; Lakaye, Bernard ULiege et al

Poster (2014, May)

For many years, our laboratory has been interested in thiamine triphosphate (ThTP), a vitamin B1 derivative whose metabolism and physiological role remain unclear. Regarding its production, we have shown ... [more ▼]

For many years, our laboratory has been interested in thiamine triphosphate (ThTP), a vitamin B1 derivative whose metabolism and physiological role remain unclear. Regarding its production, we have shown that in E. coli and in rat brain mitochondria, ThTP is synthesized from thiamine diphosphate and inorganic phosphate through a chemiosmotic mechanism involving the FoF1- ATP synthase [1, 2]. In mammalian cells, its concentration is maintained at a low level through hydrolysis by a very specific cytosolic 25-kDa thiamine triphosphatase (ThTPase) [3]. In order to gain insight in the role of ThTP and ThTPase in mammalian tissues, we decided to generate a mouse strain invalidated in 25kDa-ThTPase with the hope that these mice will accumulate ThTP in their tissues. We obtained genetically modified embryonic stem (ES) cells from the Knockout Mouse Project (KOMP) repository. In those cells, one of the 25kDa-ThTPase alleles was replaced by a construction containing the lacZ and the neomycin resistance genes. Those ES cells were microinjected in blastocysts and the chimeric blastocysts were injected in a mouse uterus to generate chimerae. However, when we bred those mice with wild type mice, the construction was never transmitted to the pups. To explain this result, we selected those chimerae that presented a sex-reversal. In those mice, all the spermatozoids derive from the injected embryonic stem cells, so that half of the spermatozoids are expected to harbor the construction. However, after qPCR analysis, we observed that the spermatozoids with the construction were outnumbered by a factor of thousand. These results strongly suggest that the 25kDa-ThTPase is required for spermatozoid development. 1. Gangolf, M., Wins, P., Thiry, M., El Moualij, B. & Bettendorff, L. (2010) J. Biol. Chem. 285, 583-94. 2. Gigliobianco, T., Gangolf, M., Lakaye, B., Pirson, B., von Ballmoos, C., Wins, P. & Bettendorff, L. (2013) Scientific reports. 3, 1071. 3. Lakaye, B., Makarchikov, A. F., Antunes, A. F., Zorzi, W., Coumans, B., De Pauw, E., Wins, P., Grisar, T. & Bettendorff, L. (2002) J. Biol. Chem. 277, 13771-7. [less ▲]

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See detailThiamine and benfotiamine improve memory, decrease depressive-like behavior and reduce brain expression of GSK3 beta in mice
Markova, N; Shevtsova, E; Vignisse, Julie ULiege et al

Poster (2014, May)

An increasing body of evidence suggests an implication of altered thiamine metabolism in mental illnesses, including depression and Alzheimer’s disease. Here, we examined the effects of a two-week ... [more ▼]

An increasing body of evidence suggests an implication of altered thiamine metabolism in mental illnesses, including depression and Alzheimer’s disease. Here, we examined the effects of a two-week treatment with thiamine (200 mg/kg/day) or benfotiamine (200 mg/kg/day, a synthetic thiamine precursor of high bioavailability, on learning of C57 mice in step down avoidance (SDA) and fear conditioning (FC) tests and depressive-like behavior in the modified forced swimming test (modFST). In addition, we investigated the effects of these drugs on brain gene expression of Glycogene Synthase Kinase 3beta (GSK3b), a regulatory factor that is involved in both above-mentioned mental conditions. Benfotiamine, but not thiamine significantly increased contextual learning in C57 mice in the step-down paradigm and acquisition of fear conditioning during weak training. Both compounds have improved the extinction of contextual fear conditioning memory and did not alter the acquisition of fear conditioning during strong training. Also, we found that both treatments reduced depressive-like behavior in mice, as shown by diminished duration of floating behavior in the modified forced swim test. With the modified forced swimming test applied here, an additional swimming session was carried out 120 hours after the first trial and resulted in increased mRNA levels of GSK3b in the prefrontal cortex, which correlated with duration of floating in tested mice. Thiamine and benfotiamine reduced GSK3b expression in the prefrontal cortex and the hippocampus that was more pronounced in the animals with low floating, in case of the measurements made in the prefrontal cortex. Together, these data suggest pro-cognitive and antidepressant-like effect of benfotiamine that are partly shared by thiamine and can be mediated by their inhibitory effect on the GSK3b [less ▲]

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See detailThiamine triphosphate: a ubiquitous molecule in search of a physiological role
Bettendorff, Lucien ULiege; Wins, Pierre

in Metabolic Brain Disease (2014), 29

Thiamine triphosphate (ThTP) was discovered over 60 years ago and it was long thought to be a specifically neuroactive compound. Its presence in most cell types, from bacteria to mammals, would suggest a ... [more ▼]

Thiamine triphosphate (ThTP) was discovered over 60 years ago and it was long thought to be a specifically neuroactive compound. Its presence in most cell types, from bacteria to mammals, would suggest a more general role but this remains undefined. In contrast to thiamine diphosphate (ThDP), ThTP is not a coenzyme. In E. coli cells, ThTP is transiently produced in response to amino acid starvation, while in mammalian cells, it is constitutively produced at a low rate. Though it was long thought that ThTP was synthesized by a ThDP:ATP phosphotransferase, more recent studies indicate that it can be synthesized by two different enzymes: (1) adenylate kinase 1 in the cytosol and (2) FoF1-ATP synthase in brain mitochondria. Both mechanisms are conserved from bacteria to mammals. Thus ThTP synthesis does not seem to require a specific enzyme. In contrast, its hydrolysis is catalyzed, at least in mammalian tissues, by a very specific cytosolic thiamine triphosphatase (ThTPase), controlling the steady-state cellular concentration of ThTP. In some tissues where adenylate kinase activity is high and ThTPase is absent, ThTP accumulates, reaching ≥ 70% of total thiamine, with no obvious physiological consequences. In some animal tissues, ThTP was able to phosphorylate proteins, and activate a high-conductance anion channel in vitro. These observations raise the possibility that ThTP is part of a still uncharacterized cellular signaling pathway. On the other hand, its synthesis by a chemiosmotic mechanism in mitochondria and respiring bacteria might suggest a role in cellular energetics. [less ▲]

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See detailConcomitant manipulation of NMDA- and AMPA-receptors to produce pro-cognitive drug effects
Vignisse, Julie ULiege; Steinbusch, Harry W.M.; Grigoriev, Vladimir et al

in European Neuropsychopharmacology (2014), 24

Bifunctional drug therapy targeting distinct receptor signaling systems can generate increased efficacy at lower concentrations compared to monofunctional therapy. Non-competitive blockade of the NMDA ... [more ▼]

Bifunctional drug therapy targeting distinct receptor signaling systems can generate increased efficacy at lower concentrations compared to monofunctional therapy. Non-competitive blockade of the NMDA receptors or the potentiation of AMPA receptors is well documented to result in memory enhancement. Here, we compared the efficacy of the low-affinity NMDA receptor blocker memantine or the positive modulator of AMPA receptor QXX (in C57BL/6J at 1 or 5 mg/kg, ip) with new derivatives of isothiourea (0.5-1 mg/kg, ip) that have bifunctional efficacy. Low-affinity NMDA blockade by these derivatives was achieved by introducing greater flexibility into the molecule, and AMPA receptor stimulation was produced by a sulfamide-containing derivative of isothiourea. Contextual learning was examined in a step-down avoidance task and extinction of contextual memory was studied in a fear-conditioning paradigm. Memantine enhanced contextual learning while QXX facilitated memory extinction; both drugs were effective at 5 mg/kg. The new derivative IPAC-5 elevated memory scores in both tasks at the dose 0.5 mg/Kg and exhibited the lowest IC50 values of NMDA receptor blockade and highest potency of AMPA receptor stimulation. Thus, among the new drugs tested, IPAC-5 plicated the properties of memantine and QXX in one administration with increased potency. Our data suggest that a concomitant manipulation of NMDA- and AMPA-receptors results in pro-cognitive effects and supports the concept bifunctional drug therapy as a promising strategy to replace monofunctional therapies with greater efficacy and improved compliance. [less ▲]

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See detailChapter 7: Thiamine
Bettendorff, Lucien ULiege

in Zemplini, Janos; Suttie, John W.; Gregory, Jesse F. (Eds.) et al Handbook of Vitamins, 5th Edition (2014)

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See detailBiological functions of thiamine derivatives: Focus on non-coenzyme roles
Bettendorff, Lucien ULiege; Wins, Pierre

in OA Biochemistry (2013), 1(1), 10

Thiamine (vitamin B1) is mainly known for its diphosphorylated derivatives (ThDP), an essential coenzyme in energy metabolism. However non-coenzyme roles have been suggested for this vitamin for many ... [more ▼]

Thiamine (vitamin B1) is mainly known for its diphosphorylated derivatives (ThDP), an essential coenzyme in energy metabolism. However non-coenzyme roles have been suggested for this vitamin for many years. Such roles have remained hypothetical, but recent data from various sources have shed a new light on this hypothesis. First, the existence of other phosphorylated thiamine derivatives, most prominently thiamine triphosphate (ThTP) and adenosine thiamine triphosphate (AThTP) can reach significant levels in E. coli, respectively during amino acid starvation and energy stress. Though much less is known about these compounds in animals, mammalian cells contain a highly specific soluble thiamine triphosphatase controlling cytosolic ThTP concentrations. Second, there is now growing evidence in favour of the existence of thiamine-binding proteins with specific roles in the nervous system, possibly in the regulation of in neurotransmitter release. Thiamine and some of its synthetic precursors with higher bioavailability have beneficial effects in several models of Alzheimer’s disease and may be beneficial for patients suffering from Alzheimer's or Parkinson's diseases. These effects might be related to non-coenzyme roles of thiamine, possibly involving thiamine-binding proteins. [less ▲]

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See detailBiochemistry of thiamine and thiamine phosphate compounds
Bettendorff, Lucien ULiege; Wins, Pierre

in Lennarz, W. J.; Lane, M. D. (Eds.) The Encyclopedia of Biological Chemistry, vol 1 (2013)

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See detailThiamine and thiazolium binding proteome includes DJ-1, amyloid beta and several membrane proteins
Bunik; Parkhomenko, Y; Kaehne, T et al

Poster (2013, March)

Detailed reference viewed: 62 (4 ULiège)