Bruno Vincent

Bruno Vincent, Ph.D.

Ph.D. (Molecular and Cellular Pharmacology), University of Nice-Sophia-Antipolis, France, 1996
Email:  bruno.vin@mahidol.ac.th
Phone: (+66) 2-441-9003-7: Ext: 1451
Research Interests : Cellular Biology and Pharmacology of Alzheimer’s DiseaseExpertise

Alzheimer’s disease (AD) is the main cause of dementia in the elderly. Because the amyloid-bpeptide (Aβ) is the major component of the senile plaques that develop in the brain of affected patients, numerous studies aimed at preventing its production were conducted during the past 25 years.

Our team is interested in the development of new therapeutic strategies aimed at fighting AD. We are particularly focusing on the regulation of the proteolytic activities (called “secretases”) that are responsible for the metabolism of the β-amyloid precursor protein (βAPP).

Our research activity can be divided in three different parts.

– First, we are investigating the capacity of hormones (melatonin), food-containing natural molecules (curcumin analogs) or compounds issued from the Thai traditional medicine (Wattana recipe) to inhibit the amyloidogenic (β-and γ-secretase) or activate the non-amyloidogenic (α-secretase) enzymes. We also hope to soon identify new molecules able to strongly and specifically target these proteases.

– Second, we are interested in the identification of new functional molecular cross-talk between secretases and in their regulation by intracellular domains (ICDs, small fragments produced by the cleavage of transmembrane proteins by γ-secretase and that can translocate into the nucleus and regulate the transcription of target genes).

– Third, we study the regulation of secretases (andbAPP processing) by some proteins a priori unrelated to AD but that have been suggested to interfere with βAPP biology. Our three proteins of interest are cyclin D1 (involved in cell cycle progression), Sox2 (a transcription factor responsible for the maintenance of neural stem cells multipotency) and NALCN (a cation channel that controls basal neuronal excitability).

Hopefully, our research will permit to unveil new tracks for future therapeutic intervention in AD.

Selected Publications

  1. Vincent, B. and Govitrapong, P. (2011). Activation of the a-secretase processing of AbPP as a therapeutic approach in Alzheimer’s disease. J. Alzheimers Dis. 24(Sup.1):75-94.
  2. Vincent, B. and Checler, F. (2012) a-secretase in Alzheimer’s disease and beyond: mechanistic, regulation and function in the shedding of membrane proteins. Curr. Alz. Res. 9:140-156.
  3. Narasingappa, R.B., Javagal, M.R., Pullabhatla, S., Htoo, H.H., Rao, J.K.S., Hernandez, J.F., Govitrapong, P. and Vincent, B. (2012). Activation of a-secretase by curcumin-aminoacid conjugates. Biochem. Biophys. Res. Commun. 424:691-696.
  4. Shukla, M., Htoo, H.H., Wintachai, P., Hernandez, J.F., Dubois, C., Postina, R., Xu, H., Checler, F., Smith, D.R., Govitrapong, P. and Vincent, B. (2015). Melatonin stimulates the non amyloidogenic processing of bAPP through the positive transcriptional regulation of ADAM10 and ADAM17. J. Pineal Res. 58:151-165.
  5. Sarlak, G., Htoo, H.H., Hernandez, J.F., Iizasa, H., Checler, F., Konietzko, U., Song, W. and Vincent, B. (2016). Sox2 functionally interacts with bAPP, the bAPP intracellular domain and ADAM10 at a transcriptional level in human cells. Neuroscience 312:153-164.
  6. Sarlak, G. and Vincent, B. (2016). The roles of the stem cell-controlling Sox2 transcription factor: from neuroectoderm development to Alzheimer’s disease? Mol. Neurobiol. (in press).
  7. Vincent B. (2016). Regulation of the a-secretase ADAM10 at transcriptional, translational and post-translational levels. Brain Res. Bull. 126, 154-169.
  8. Htoo H.H., Limsuvan S., Thamsermsang O., Hernandez J.F., Checler F., Govitrapong P., Pakaprot N., Akarasereenont P. and Vincent B. (2017). The polyherbal Wattana formula displays anti-amyloidogenic properties by increasing a-secretase activities. PLoS ONE 12(1):e0170360.

Full Publications

  1. Sarlak, G. and Vincent, B. (2016). The roles of the stem cell-controlling Sox2 transcription factor: from neuroectoderm development to Alzheimer’s disease? Mol. Neurobiol. (in press).
  2. Sarlak, G., Htoo, H.H., Hernandez, J.F., Iizasa, H., Checler, F., Konietzko, U., Song, W. and Vincent, B. (2016). Sox2 functionally interacts with bAPP, the bAPP intracellular domain and ADAM10 at a transcriptional level in human cells. Neuroscience 312:153-164.
  3. Panmanee, J., Nopparat, C., Chawanich, N., Shukla, M., Mukda, S., Song, W., Vincent, B. and Govitrapong, P. (2015). Melatonin regulates the transcription of bAPP-cleaving secretases mediated through melatonin receptors in human SH-SY5Y cells. J. Pineal. Res. 59:308-320.
  4. Shukla, M., Htoo, H.H., Wintachai, P., Hernandez, J.F., Dubois, C., Postina, R., Xu, H., Checler, F., Smith, D.R., Govitrapong, P. and Vincent, B. (2015). Melatonin stimulates the non amyloidogenic processing of bAPP through the positive transcriptional regulation of ADAM10 and ADAM17. J. Pineal Res. 58:151-165.
  5. Vincent, B., Cissé, M., Sunyach, C., Guillot-Sestier, M.V. and Checler F. (2013) The regulation of bAPP and PrPc processing by a-secretase. Adv. Alz. Res. 1:81-104.
  6. Narasingappa, R.B., Javagal, M.R., Pullabhatla, S., Htoo, H.H., Rao, J.K.S., Hernandez, J.F., Govitrapong, P. and Vincent, B. (2012). Activation of a-secretase by curcumin-aminoacid conjugates. Biochem. Biophys. Res. Commun. 424:691-696.
  7. Vincent, B. and Checler, F. (2012). a-secretase in Alzheimer’s disease and beyond: mechanistic, regulation and function in the shedding of membrane proteins. Curr. Alz. Res. 9:140-156.
  8. Cissé, M., Duplan, E., Guillot-Sestier, M.V., Rumigny, J., Bauer, C., Pages, G., Orzechowski, H.D., Slack, B.E., Checler, F. and Vincent, B. (2011). The extracellular regulated kinase-1 (ERK1) controls regulated a-secretase-mediated processing, promoter transactivation and mRNA levels of the cellular prion protein. J. Biol. Chem. 286(33):29192-29206.
  9. Cissé, M., Braun, U., Leitges, M., Fisher, A., Pages, G., Checler, F. and Vincent, B. (2011). ERK1-independent a-secretase cut of b-amyloid precursor protein via M1 muscarinic receptors and PKCa/e. Mol. Cell. Neurosci. 47:223-232.
  10. Vincent B. and Govitrapong P. (2011). Activation of the a-secretase processing of AbPP as a therapeutic approach in Alzheimer’s disease. J. Alzheimers Dis. 24(Sup.1):75-94.
  11. Vincent, B., Sunyach, C., Orzechowski, HD., St Georges-Hyslop, P and Checler, F. (2009). p53-dependent transcriptional regulation of cellular prion by presenilins. J. Neurosci. 29(20):6752-6760.
  12. Vincent, B., Alfa Cissé, M. and Checler, F. (2008). Physiological processing of the cellular prion protein and bAPP: enzymes and regulation. Advances in Alzheimer’s and Parkinson’s Diseases. 57:305-316.
  13. Alfa Cissé M., Louis K., Braun U., Mari B., Leitges M., Slack B.E., Fisher A., Auberger P., Checler F. and Vincent B. (2008). Isoform-specific contribution of protein kinase C to prion processing.  Mol. Cell. Neurosci. 39:400-410.
  14. Vincent, B., Alfa Cissé, M., Sunyach, C., Guillot-Sestier, M.V. and Checler F. (2008). Regulation of bAPP and PrPc cleavage by a-secretase: mechanistic and therapeutic perspectives. Curr. Alz. Res. 5:202-211.
  15. Checler, F., Sunyach, C., Pardossi-Piquard, R., Sévalle, J., Vincent, B., Kawarai, T., Girardot, N., St. Georges-Hyslop, P. and Alves da Costa, C. (2007). The g/e-secretase-derived APP intracellular domain fragments regulate p53. Curr. Alz. Res. 4:423-426.
  16. Alfa Cissé., M, Sunyach, C., Slack, B.E., Fisher, A., Vincent, B. and Checler, F. (2007). M1 and M3 muscarinic receptors control physiological processing of cellular prion by modulating ADAM17 phosphorylation and activity. J. Neurosci. 27(15):4083-4092.
  17. Pardossi-Piquard, R., Dunys, J., Kawarai, T., Sunyach, C., Alves da Costa, C., Vincent, B., Sévalle, J., Pimplikar, S., St. Georges-Hyslop, P. and Checler, F. (2007).  Response to correspondence: Pardossi-Piquardet al., “Presenilin-dependent transcriptional control of the Ab-degrading enzyme neprilysin by intracellular domains of bAPP and APLP.” Neuron 53:483-486.
  18. Sunyach, C., Alfa Cissé, M., Alves da Costa, C., Vincent, B. and Checler, F. (2007). The C-terminal products of cellular prion protein processing, C1 and C2, exert distinct influence on p53-dependent staurosporine-induced caspase-3 activation. J. Biol. Chem. 282(3):1956-1963.
  19. Alfa Cissé, M., Gandreuil, C., Hernandez, J.F., Martinez, J., Checler, F. and Vincent, B. (2006). Design and characterization of a novel cellular prion-derived quenched fluorimetric substrate of a-secretase. Biochem. Biophys. Res. Commun. 347:254-260.
  20. Alves da Costa, C., Sunyach, C., Pardossi-Piquard, R., Sévalle, J., Vincent, B., Boyer, N., Kawarai, T., Girardot, N., St. Georges Hyslop, P. and Checler, F. (2006) .Presenilin-dependent g-secretase-mediated control of p53-associated cell death in Alzheimer’s disease. J. Neurosci. 26(23):6377-6385.
  21. Alfa Cissé, M., Sunyach, C., Lefranc-Jullien, S., Postina, R., Vincent, B. and Checler, F. (2005). The disintegrin ADAM9 indirectly contributes to the physiological processing of cellular prion by modulating ADAM10 activity. J. Biol. Chem. 280(49):40624-40631.
  22. Pardossi-Piquard, R., Petit, A., Kawarai, T., Sunyach, C., Alves da Costa, C., Vincent, B., Ring, S., D’Adamio, L., Shen, J., Müller, U., St. Georges Hyslop, P. and Checler, F. (2005). Presenilin-dependent transcriptional control of the Ab-degrading enzyme neprilysin by intracellular domains of bAPP and APLP. Neuron 46:541-554.
  23. Vincent, B. (2004). ADAM proteases: protective role in Alzheimer’s and prion diseases? Curr. Alz. Res. 1:165-174.
  24. Paitel, E., Sunyach, C., Alves da Costa, C., Bourdon, J.C., Vincent, B. and Checler, F. (2004). Primary cultured neurons devoid of cellular prion display lower responsiveness to staurosporine through the control of p53 at both transcriptional and post-transcriptional levels. J. Biol. Chem. 279(1):612-618.
  25. Alves da Costa, C., Paitel, E., Vincent, B. and Checler, F. (2002). a-synuclein lowers p53-dependent apoptotic response of neuronal cells. J. Biol. Chem. 277(52):50980-50984.
  26. Checler, F. and Vincent, B. (2002). Alzheimer’s and prion diseases: distinct pathologies, common proteolytic denominators. Trends in Neurosci. 25(12):616-620.
  27. Checler, F., Alves da Costa, C., Ancolio, K., Chevallier, N., Dumanchin-Njock, C., Lopez-Perez, E., Marambaud, P., Paitel, E., Petit, A. and Vincent, B. (2002). Métabolisme du précurseur du peptide amyloïde et présénilines. Médecine/Science 18:717-724.
  28. Petit, A., Vincent, B., Scarzello, S., Armogida, M., Alves da Costa, C. and Checler, F. (2002). Endogenous Abproduction is not affected by presenilins deficiency in fibroblasts. Nature Cell Biol. 4:E165-E166.
  29. Armogida, M., Petit, A., Vincent, B., Scarzello, S., Alves da Costa, C. and Checler, F. (2001). Endogenous b-amyloid production in presenilin-deficient embryonic mouse fibroblasts. Nature Cell Biol. 3:1030-1033.
  30. Vincent, B., Paitel, E., Saftig, P., Frobert, Y., Hartmann, D., De Strooper, B., Grassi, J., Lopez-Perez, E. and Checler, F. (2001).  The disintegrins ADAM10 and TACE contribute to the constitutive and phorbol-ester-regulated normal cleavage of the cellular prion protein. J. Biol. Chem. 276(41):37743-37746.
  31. Vincent, B. and Smith, J.D. (2001). Astrocytes regulate neuronal b-amyloid precursor protein expression and modify its processing in an apolipoprotein E isoform-specific manner. Eur. J. Neurosci. 14:256-266.
  32. Vincent, B., Paitel, E., Frobert, Y., Lehmann, S., Grassi, J. and Checler, F. (2000). Phorbol ester-regulated cleavage of normal prion protein in HEK293 human cells and murine neurons. J. Biol. Chem. 275(45):35612-35616.
  33. Vincent, B. and Smith, J.D. (2000). Effect of estradiol on neuronal Swedish-mutated b-amyloid precursor protein metabolism: reversal by astrocytic cells. Biochem. Biophys. Res. Commun. 271(1):82-85.
  34. Gouras, G.K., Tsai, J., Naslund, J., Vincent, B., Edgar, M., Checler, F., Greenfield, J.P., Haroutunian, V., Buxbaum, J.D., Xu, H., Greengard, P. and Relkin, N.R. (2000). Intraneuronal Ab42 accumulation in human brain. Am. J. Pathol. 156(1):15-20.
  35. Garrido, P.A.G, Vandenbulcke, F., Ramjaun, A.R., Vincent, B., Checler, F., Ferro, E. and Beaudet, A. (1999). Confocal microscopy reveals thimet oligopeptidase (EC 3.4.24.15) and neurolysin (EC 3.4.24.16) in the classical secretory pathway. DNA Cell Biol. 18(4):323-331.
  36. Rioli, V., Kato, A., Portaro, F.C.V., Cury, G.K., TeKaat, K., Vincent, B., Checler, F., Camargo, A.C.M., Glucksman, M.J., Roberts, J.L., Hirose, S. and Ferro, E.S. (1998). Neuropeptide specificity and inhibition of recombinant isoforms of the endopeptidase 3.4.24.16 family: comparison with the related recombinant endopeptidase 3.4.24.15. Biochem. Biophys. Res. Commun. 250:5-11.
  37. Xu, H., Gouras, G.K., Greenfield, J.P., Vincent, B., Naslund, J., Mazzarelli, L., Fried, G., Jovanovic, J.N., Seeger, M., Relkin, N.R., Liao, F., Checler, F., Buxbaum, J.D., Chait, B.T., Thinakaran, G., Sisodia, S.S., Wang, R., Greengard, P. and Gandy, S. (1998). Estrogen reduces neuronal generation of Alzheimer b-amyloid peptides. Nature Med. 4(4):447-451.
  38. Buxbaum, J.D., Ikin, A., Luo, Y., Naslund, J., Sabo, S., Vincent, B., Watanabe, T. and Greengard, P. (1998). APP localization and trafficking in the central nervous system. Progress in Alzheimer’s and Parkinson’s Diseases 49:487-494.
  39. Buxbaum, J.D., Ikin, A., Luo, Y., Naslund, J., Sabo, S., Vincent, B., Watanabe, T. and Greengard, P. (1998). Regulation of APP metabolism by protein phosphorylation. Progress in Alzheimer’s and Parkinson’s Diseases 49:133-140.
  40. Vincent, B., Jiracek, J., Noble, F., Loog, M., Roques, B., Dive, V., Vincent, J.P. and Checler, F. (1997). Contribution of endopeptidase 3.4.24.15 to central neurotensin inactivation. Eur. J. Pharmacol. 334:49-53.
  41. Vincent, B., Jiracek, J., Noble, F., Loog, M., Roques, B., Dive, V., Vincent, J.P. and Checler, F. (1997). A novel selective and potent phosphinic peptide inhibitor of endopeptidase 3.4.24.16: effect on neurotensin-induced analgesia and neuronal inactivation. Brit. J. Pharmacol. 121:705-710.
  42. Chevallier, N., Jiracek, J., Vincent, B., Ichai, C., Vincent, J.P. and Checler, F. (1997). Examination of the role of endopeptidase 3.4.24.15 in Abformation by human transfected cells. Brit. J. Pharmacol. 121:556-562.
  43. Vincent, B., Dauch, P., Vincent, J.P. and Checler, F. (1997). Stably transfected human cells expressing rat brain endopeptidase 3.4.24.16: biochemical characterization of the activity and expression of a membrane-bound counterpart. J. Neurochem. 68:837-845.
  44. Vincent, B., Beaudet, A., Dauch, P., Vincent, J.P. and Checler, F. (1996). Distinct properties of neuronal and astrocytic endopeptidase 3.4.24.16: a study on differentiation, subcellular distribution and secretion processes. J. Neurosci. 16(16):5049-5059.
  45. Jiracek, J., Yiotakis, A., Vincent, B., Checler, F. and Dive, V. (1996). Development of the first potent and selective inhibitor of the zinc endopeptidase neurolysin using a systematic approach based on combinatorial chemistry of phosphinic peptides. J. Biol. Chem. 271(32):19606-19611.
  46. Vincent, B., Vincent, J.P. and Checler, F. (1996). Purification and characterization of human endopeptidase 3.4.24.16. Comparison with the porcine counterpart indicates a unique cleavage site on neurotensin. Brain Res. 709:51-58.
  47. Jiracek, J., Yiotakis, A., Vincent, B., Lecoq, A., Nicolaou, A., Checler, F. and Dive, V. (1995). Development of highly potent and selective phosphinic peptide inhibitors of the zinc endopeptidase 24-15 using combinatorial chemistry. J. Biol. Chem. 270(37):21701-21706.
  48. Checler, F., Barelli, H., Dauch, P., Dive, V., Vincent, B. and Vincent, J.P. (1995). Endopeptidase 3.4.24.16 (Neurolysin): Purification and assays. Methods in enzymology 248:593-614.
  49. Vincent, B., Dive, V., Yiotakis, A., Smadja, C., Maldonado, R., Vincent, J.P. and Checler, F. (1995). Phosphorus-containing peptides as mixed inhibitors of endopeptidase 3.4.24.15 and 3.4.24.16: effect on neurotensin degradation in vitro and in vivo. Brit. J. Pharmacol. 115:1053-1063.
  50. Checler, F., Dauch, P., Barelli, H., Dive, V., Masuo, Y., Vincent, B. and Vincent, J.P. (1995). Identification and distribution of endopeptidase EC 3.4.24.16 in the central nervous system. Methods in neuroscience 23:363-382.
  51. Vincent, B., Vincent, J.P. and Checler, F. (1994). Neurotensin and neuromedin N undergo distinct catabolic processes in murine astrocytes and primary cultured neurons. Eur. J. Biochem. 221:297-306.
  52. Checler, F., Barelli, H., Dauch, P., Vincent, B., Dive, V., Beaudet, A., Daniel, E.E., Fox-Threkeld, J.E.T., Masuo, Y. and Vincent, J.P. (1993). Recent advances on endopeptidase 3.4.24.16. Biochem. Soc. Trans. 21:692-698.
  53. Barelli, H., Mao, Y.K., Vincent, B., Daniel, E.E., Vincent,J.P. and Checler, F. (1993). Differential catabolic fate of neuromedin N and neurotensin in the canine intestinal mucosa. Peptides 14:457-463.

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