Skip to main content
Erschienen in: Neurological Sciences 6/2012

01.12.2012 | Original Article

DAPT protects brain against cerebral ischemia by down-regulating the expression of Notch 1 and Nuclear factor kappa B in rats

verfasst von: Shuya Li, Xiangjian Zhang, Yongjun Wang, Hui Ji, Yuanyuan Du, Haichao Liu

Erschienen in: Neurological Sciences | Ausgabe 6/2012

Einloggen, um Zugang zu erhalten

Abstract

Gamma-secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT) suppresses the activation of Notch 1 signaling, which is recognized as the cell fate signaling and may participate in inflammatory processes together with NF-κB pathway that contributes to the brain damage after stroke. DAPT has important pharmacological roles in many diseases. However, little is known about the effect of DAPT on NF-κB during cerebral ischemia. This study investigated the time course expression of Notch 1 and the effects of DAPT on Notch 1 and NF-κB after MCAO. The results showed that Notch 1 signaling was up-regulated at the early stage after MCAO, DAPT down-regulated the expression of Notch 1 and NF-κB and protected brain from damage caused by MCAO. These results may indicate that the downregulation of Notch 1–NF-κB pathway after ischemia by administration of DAPT is a potential mechanism for its protection.
Literatur
1.
Zurück zum Zitat Artavanis–Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284:770–776PubMedCrossRef Artavanis–Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284:770–776PubMedCrossRef
2.
Zurück zum Zitat De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A, Kopan R (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398:518–522PubMedCrossRef De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A, Kopan R (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398:518–522PubMedCrossRef
3.
Zurück zum Zitat Dovey HF, John V, Anderson JP, Chen LZ, de Saint Andrieu P, Fang LY, Freedman SB, Folmer B, Goldbach E, Holsztynska EJ, Hu KL, Johnson–Wood KL, Kennedy SL, Kholodenko D, Knops JE, Latimer LH, Lee M, Liao Z, Lieberburg IM, Motter RN, Mutter LC, Nietz J, Quinn KP, Sacchi KL, Seubert PA, Shopp GM, Thorsett ED, Tung JS, Wu J, Yang S, Yin CT, Schenk DB, May PC, Altstiel LD, Bender MH, Boggs LN, Britton TC, Clemens JC, Czilli DL, Dieckman-McGinty DK, Droste JJ, Fuson KS, Gitter BD, Hyslop PA, Johnstone EM, Li WY, Little SP, Mabry TE, Miller FD, Audia JE (2001) Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem 76:173–181PubMedCrossRef Dovey HF, John V, Anderson JP, Chen LZ, de Saint Andrieu P, Fang LY, Freedman SB, Folmer B, Goldbach E, Holsztynska EJ, Hu KL, Johnson–Wood KL, Kennedy SL, Kholodenko D, Knops JE, Latimer LH, Lee M, Liao Z, Lieberburg IM, Motter RN, Mutter LC, Nietz J, Quinn KP, Sacchi KL, Seubert PA, Shopp GM, Thorsett ED, Tung JS, Wu J, Yang S, Yin CT, Schenk DB, May PC, Altstiel LD, Bender MH, Boggs LN, Britton TC, Clemens JC, Czilli DL, Dieckman-McGinty DK, Droste JJ, Fuson KS, Gitter BD, Hyslop PA, Johnstone EM, Li WY, Little SP, Mabry TE, Miller FD, Audia JE (2001) Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem 76:173–181PubMedCrossRef
4.
Zurück zum Zitat Sastre M, Steiner H, Fuchs K, Capell A, Multhaup G, Condron MM, Teplow DB, Haass C (2001) Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein at a site corresponding to the S3 cleavage of Notch. EMBO Rep 2:835–841PubMedCrossRef Sastre M, Steiner H, Fuchs K, Capell A, Multhaup G, Condron MM, Teplow DB, Haass C (2001) Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein at a site corresponding to the S3 cleavage of Notch. EMBO Rep 2:835–841PubMedCrossRef
5.
Zurück zum Zitat Geling A, Steiner H, Willem M, Bally-Cuif L, Haass C (2002) A gamma-secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish. EMBO Rep 3:688–694PubMedCrossRef Geling A, Steiner H, Willem M, Bally-Cuif L, Haass C (2002) A gamma-secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish. EMBO Rep 3:688–694PubMedCrossRef
6.
Zurück zum Zitat El Mouedden M, Vandermeeren M, Meert T, Mercken M (2006) Reduction of Abeta levels in the Sprague Dawley rat after oral administration of the functional gamma-secretase inhibitor, DAPT: a novel non-transgenic model for Abeta production inhibitors. Curr Pharm Des 12:671–676PubMedCrossRef El Mouedden M, Vandermeeren M, Meert T, Mercken M (2006) Reduction of Abeta levels in the Sprague Dawley rat after oral administration of the functional gamma-secretase inhibitor, DAPT: a novel non-transgenic model for Abeta production inhibitors. Curr Pharm Des 12:671–676PubMedCrossRef
7.
Zurück zum Zitat Roberson ED, Mucke L (2006) 100 years and counting: prospects for defeating Alzheimer’s disease. Science 314:781–784PubMedCrossRef Roberson ED, Mucke L (2006) 100 years and counting: prospects for defeating Alzheimer’s disease. Science 314:781–784PubMedCrossRef
8.
Zurück zum Zitat Oya S, Yoshikawa G, Takai K, Tanaka JI, Higashiyama S, Saito N, Kirino T, Kawahara N (2009) Attenuation of Notch signaling promotes the differentiation of neural progenitors into neurons in the hippocampal CA1 region after ischemic injury. Neuroscience 158:683–692PubMedCrossRef Oya S, Yoshikawa G, Takai K, Tanaka JI, Higashiyama S, Saito N, Kirino T, Kawahara N (2009) Attenuation of Notch signaling promotes the differentiation of neural progenitors into neurons in the hippocampal CA1 region after ischemic injury. Neuroscience 158:683–692PubMedCrossRef
9.
Zurück zum Zitat Hellström M, Phngm LK, Hofmann JJ, Wallgard E, Coultas L, Lindblom P, Alva J, Nilsson AK, Karlsson L, Gaiano N, Yoon K, Rossant J, Iruela–Arispe ML, Kalén M, Gerhardt H, Betsholtz C (2007) Dll4 signalling through Notch 1 regulates formation of tip cells during angiogenesis. Nature 445:776–780PubMedCrossRef Hellström M, Phngm LK, Hofmann JJ, Wallgard E, Coultas L, Lindblom P, Alva J, Nilsson AK, Karlsson L, Gaiano N, Yoon K, Rossant J, Iruela–Arispe ML, Kalén M, Gerhardt H, Betsholtz C (2007) Dll4 signalling through Notch 1 regulates formation of tip cells during angiogenesis. Nature 445:776–780PubMedCrossRef
10.
Zurück zum Zitat Campbell KJ, Perkins ND (2006) Regulation of NF-kappa B function. Biochem Soc Symp 73(2006):165–180PubMed Campbell KJ, Perkins ND (2006) Regulation of NF-kappa B function. Biochem Soc Symp 73(2006):165–180PubMed
11.
Zurück zum Zitat Perkins ND (2007) Integrating cell-signalling pathways with NF-kappaB and IKK function. Natl Rev Mol Cell Biol 8:49–62CrossRef Perkins ND (2007) Integrating cell-signalling pathways with NF-kappaB and IKK function. Natl Rev Mol Cell Biol 8:49–62CrossRef
12.
Zurück zum Zitat Liu Y, Zhang XJ, Yang CH, Fan HG (2009) Oxymatrine protects rat brains against permanent focal ischemia and downregulates NF-κB expression. Brain Res 1268:174–180PubMedCrossRef Liu Y, Zhang XJ, Yang CH, Fan HG (2009) Oxymatrine protects rat brains against permanent focal ischemia and downregulates NF-κB expression. Brain Res 1268:174–180PubMedCrossRef
13.
Zurück zum Zitat Ang HL, Tergaonkar V (2007) Notch and NF kappa B signaling pathways: do they collaborate in normal vertebrate brain development and function? Bioessays 29:1039–1047PubMedCrossRef Ang HL, Tergaonkar V (2007) Notch and NF kappa B signaling pathways: do they collaborate in normal vertebrate brain development and function? Bioessays 29:1039–1047PubMedCrossRef
14.
Zurück zum Zitat Osipo C, Golde TE, Osborne BA, Miele LA (2008) Off the beaten pathway: the complex cross talk between Notch and NF-kappaB. Lab Invest 88(2008):11–17PubMedCrossRef Osipo C, Golde TE, Osborne BA, Miele LA (2008) Off the beaten pathway: the complex cross talk between Notch and NF-kappaB. Lab Invest 88(2008):11–17PubMedCrossRef
15.
Zurück zum Zitat Longa EZ, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91PubMedCrossRef Longa EZ, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91PubMedCrossRef
16.
Zurück zum Zitat Yang CH, Zhang XJ, Fan HG, Liu Y (2009) Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia. Brain Res 1282:133–141PubMedCrossRef Yang CH, Zhang XJ, Fan HG, Liu Y (2009) Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia. Brain Res 1282:133–141PubMedCrossRef
17.
Zurück zum Zitat Hatashita S, Hoff JT, Salamat SM (1988) Ischemic brain edema and the osmotic gradient between blood and brain. J Cereb Blood Flow Metab 8:552–559PubMedCrossRef Hatashita S, Hoff JT, Salamat SM (1988) Ischemic brain edema and the osmotic gradient between blood and brain. J Cereb Blood Flow Metab 8:552–559PubMedCrossRef
18.
Zurück zum Zitat Tatlisumak T, Carano RA, Takano K, Opgenorth TJ, Sotak CH, Fisher M (1998) A novel endothelin antagonist, A-127722, attenuates ischemic lesion size in rats with temporary middle cerebral artery occlusion: a diffusion and perfusion MRI study. Stroke 29(1998):850–857PubMedCrossRef Tatlisumak T, Carano RA, Takano K, Opgenorth TJ, Sotak CH, Fisher M (1998) A novel endothelin antagonist, A-127722, attenuates ischemic lesion size in rats with temporary middle cerebral artery occlusion: a diffusion and perfusion MRI study. Stroke 29(1998):850–857PubMedCrossRef
19.
Zurück zum Zitat de la Pompa JL, Wakeham A, Correia KM, Samper E, Brown S, Aguilera RJ, Nakano T, Honjo T, Mak TW, Rossant J, Conlon RA (1997) Conservation of the Notch signalling pathway in mammalian neurogenesis. Development 124:1139–1148PubMed de la Pompa JL, Wakeham A, Correia KM, Samper E, Brown S, Aguilera RJ, Nakano T, Honjo T, Mak TW, Rossant J, Conlon RA (1997) Conservation of the Notch signalling pathway in mammalian neurogenesis. Development 124:1139–1148PubMed
20.
Zurück zum Zitat Hitoshi S, Alexson T, Tropepe V, Donoviel D, Elia AJ, Nye JS, Conlon RA, Mak TW, Bernstein A, van der Kooy D (2002) Notch pathway molecules are essential for the maintenance, but not the generation, of mammalian neural stem cells. Genes Dev 16(2002):846–858PubMedCrossRef Hitoshi S, Alexson T, Tropepe V, Donoviel D, Elia AJ, Nye JS, Conlon RA, Mak TW, Bernstein A, van der Kooy D (2002) Notch pathway molecules are essential for the maintenance, but not the generation, of mammalian neural stem cells. Genes Dev 16(2002):846–858PubMedCrossRef
21.
Zurück zum Zitat Gustafsson MV, Zheng X, Pereira T, Gradin K, Jin S, Lundkvist J, Ruas JL, Poellinger L, Lendahl U, Bondesson M (2005) Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell 9:617–628PubMedCrossRef Gustafsson MV, Zheng X, Pereira T, Gradin K, Jin S, Lundkvist J, Ruas JL, Poellinger L, Lendahl U, Bondesson M (2005) Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell 9:617–628PubMedCrossRef
22.
Zurück zum Zitat Yoon K, Gaiano N (2005) Notch signaling in the mammalian central nervous system: insights from mouse mutants. Nat Neurosci 8:709–715PubMedCrossRef Yoon K, Gaiano N (2005) Notch signaling in the mammalian central nervous system: insights from mouse mutants. Nat Neurosci 8:709–715PubMedCrossRef
23.
Zurück zum Zitat Androutsellis–Theotokis A, Leker RR, Soldner F, Hoeppner DJ, Ravin R, Poser SW, Rueger MA, Bae SK, Kittappa R, McKay RD (2006) Notch signalling regulates stem cell numbers in vitro and in vivo. Nature 442:823–826PubMedCrossRef Androutsellis–Theotokis A, Leker RR, Soldner F, Hoeppner DJ, Ravin R, Poser SW, Rueger MA, Bae SK, Kittappa R, McKay RD (2006) Notch signalling regulates stem cell numbers in vitro and in vivo. Nature 442:823–826PubMedCrossRef
24.
Zurück zum Zitat Mizutani K, Yoon K, Dang L, Tokunaga A, Gaiano N (2007) Differential Notch signalling distinguishes neural stem cells from intermediate progenitors. Nature 449:351–356PubMedCrossRef Mizutani K, Yoon K, Dang L, Tokunaga A, Gaiano N (2007) Differential Notch signalling distinguishes neural stem cells from intermediate progenitors. Nature 449:351–356PubMedCrossRef
25.
Zurück zum Zitat Wolfer A, Wilson A, Nemir M, MacDonald HR, Radtke F (2002) Inactivation of Notch 1 impairs VDJbeta rearrangement and allows pre-TCR-independent survival of early alpha beta Lineage Thymocytes. Immunity 16:869–879PubMedCrossRef Wolfer A, Wilson A, Nemir M, MacDonald HR, Radtke F (2002) Inactivation of Notch 1 impairs VDJbeta rearrangement and allows pre-TCR-independent survival of early alpha beta Lineage Thymocytes. Immunity 16:869–879PubMedCrossRef
26.
Zurück zum Zitat Maillard I, Tu L, Sambandam A, Yashiro-Ohtani Y, Millholland J, Keeshan K, Shestova O, Xu L, Bhandoola A, Pear WS (2006) The requirement for Notch signaling at the beta-selection checkpoint in vivo is absolute and independent of the pre-T cell receptor. J Exp Med 203b:2239–2245CrossRef Maillard I, Tu L, Sambandam A, Yashiro-Ohtani Y, Millholland J, Keeshan K, Shestova O, Xu L, Bhandoola A, Pear WS (2006) The requirement for Notch signaling at the beta-selection checkpoint in vivo is absolute and independent of the pre-T cell receptor. J Exp Med 203b:2239–2245CrossRef
27.
Zurück zum Zitat Teachey DT, Seif AE, Brown M, Bruno M, Bunte RM, Chang YJ, Choi JK, Fish JD, Hall J, Reid GS, Ryan T, Sheen C, Zweidler-McKay P, Grupp SA (2008) Targeting Notch signaling in autoimmune and lymphoproliferative disease. Blood 111:705–714PubMedCrossRef Teachey DT, Seif AE, Brown M, Bruno M, Bunte RM, Chang YJ, Choi JK, Fish JD, Hall J, Reid GS, Ryan T, Sheen C, Zweidler-McKay P, Grupp SA (2008) Targeting Notch signaling in autoimmune and lymphoproliferative disease. Blood 111:705–714PubMedCrossRef
28.
Zurück zum Zitat Weng AP, Ferrando AA, Lee W, Morris JP 4th, Silverman LB, Sanchez-Irizarry C, Blacklow SC, Look AT, Aster JC (2004) Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 306:269–271PubMedCrossRef Weng AP, Ferrando AA, Lee W, Morris JP 4th, Silverman LB, Sanchez-Irizarry C, Blacklow SC, Look AT, Aster JC (2004) Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 306:269–271PubMedCrossRef
29.
Zurück zum Zitat Fung E, Tang SM, Canner JP, Morishige K, Arboleda-Velasquez JF, Cardoso AA, Carlesso N, Aster JC, Aikawa M (2007) Delta-Like 4 Induces notch signaling in macrophages: implications for inflammation. Circulation 115:2948–2956PubMedCrossRef Fung E, Tang SM, Canner JP, Morishige K, Arboleda-Velasquez JF, Cardoso AA, Carlesso N, Aster JC, Aikawa M (2007) Delta-Like 4 Induces notch signaling in macrophages: implications for inflammation. Circulation 115:2948–2956PubMedCrossRef
30.
Zurück zum Zitat Arumugam TV, Chan SL, Jo DG, Yilmaz G, Tang SC, Cheng A, Gleichmann M, Okun E, Dixit VD, Chigurupati S, Mughal MR, Ouyang X, Miele L, Magnus T, Poosala S, Granger DN, Mattson MP (2006) Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke. Nat Med 12:621–623PubMedCrossRef Arumugam TV, Chan SL, Jo DG, Yilmaz G, Tang SC, Cheng A, Gleichmann M, Okun E, Dixit VD, Chigurupati S, Mughal MR, Ouyang X, Miele L, Magnus T, Poosala S, Granger DN, Mattson MP (2006) Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke. Nat Med 12:621–623PubMedCrossRef
31.
Zurück zum Zitat Bash J, Zong WX, Banga S, Rivera A, Ballard DW, Ron Y, Gelinas C (1999) Rel/NF-kappaB can trigger the Notch signaling pathway by inducing the expression of Jagged1, a ligand for Notch receptors. EMBO J 18:2803–2811PubMedCrossRef Bash J, Zong WX, Banga S, Rivera A, Ballard DW, Ron Y, Gelinas C (1999) Rel/NF-kappaB can trigger the Notch signaling pathway by inducing the expression of Jagged1, a ligand for Notch receptors. EMBO J 18:2803–2811PubMedCrossRef
32.
Zurück zum Zitat Nickoloff BJ, Qin JZ, Chaturvedi V, Denning MF, Bonish B, Miele L (2002) Jagged-1 mediated activation of notch signaling induces complete maturation of human keratinocytes through NF-kappaB and PPARgamma. Cell Death Differ 9:842–855PubMedCrossRef Nickoloff BJ, Qin JZ, Chaturvedi V, Denning MF, Bonish B, Miele L (2002) Jagged-1 mediated activation of notch signaling induces complete maturation of human keratinocytes through NF-kappaB and PPARgamma. Cell Death Differ 9:842–855PubMedCrossRef
33.
Zurück zum Zitat Espinosa L, Ingles-Esteve J, Robert-Moreno A, Bigas A (2003) IkappaBalpha and p65 regulate the cytoplasmic shuttling of nuclear corepressors: cross-talk between Notch and NFkappaB pathways. Mol Biol Cell 14:491–502PubMedCrossRef Espinosa L, Ingles-Esteve J, Robert-Moreno A, Bigas A (2003) IkappaBalpha and p65 regulate the cytoplasmic shuttling of nuclear corepressors: cross-talk between Notch and NFkappaB pathways. Mol Biol Cell 14:491–502PubMedCrossRef
34.
Zurück zum Zitat Yao J, Duan L, Fan M, Wu X (2007) Gamma-secretase inhibitors exerts antitumor activity via down–regulation of Notch and Nuclear factor kappa B in human tongue carcinoma cells. Oral Dis 13:555–563PubMedCrossRef Yao J, Duan L, Fan M, Wu X (2007) Gamma-secretase inhibitors exerts antitumor activity via down–regulation of Notch and Nuclear factor kappa B in human tongue carcinoma cells. Oral Dis 13:555–563PubMedCrossRef
35.
Zurück zum Zitat Mayer SC, Kreft AF, Harrison B, Abou-Gharbia M, Antane M, Aschmies S, Atchison K, Chlenov M, Cole DC, Comery T, Diamantidis G, Ellingboe J, Fan K, Galante R, Gonzales C, Ho DM, Hoke ME, Hu Y, Huryn D, Jain U, Jin M, Kremer K, Kubrak D, Lin M, Lu P, Magolda R, Martone R, Moore W, Oganesian A, Pangalos MN, Porte A, Reinhart P, Resnick L, Riddell DR, Sonnenberg-Reines J, Stock JR, Sun SC, Wagner E, Wang T, Woller K, Xu Z, Zaleska MM, Zeldis J, Zhang M, Zhou H, Jacobsen JS (2008) Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer’s disease. J Med Chem 51:7348–7351PubMedCrossRef Mayer SC, Kreft AF, Harrison B, Abou-Gharbia M, Antane M, Aschmies S, Atchison K, Chlenov M, Cole DC, Comery T, Diamantidis G, Ellingboe J, Fan K, Galante R, Gonzales C, Ho DM, Hoke ME, Hu Y, Huryn D, Jain U, Jin M, Kremer K, Kubrak D, Lin M, Lu P, Magolda R, Martone R, Moore W, Oganesian A, Pangalos MN, Porte A, Reinhart P, Resnick L, Riddell DR, Sonnenberg-Reines J, Stock JR, Sun SC, Wagner E, Wang T, Woller K, Xu Z, Zaleska MM, Zeldis J, Zhang M, Zhou H, Jacobsen JS (2008) Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer’s disease. J Med Chem 51:7348–7351PubMedCrossRef
36.
Zurück zum Zitat Tammam J, Ware C, Efferson C, O’Neil J, Rao S, Qu X, Gorenstein J, Angagaw M, Kim H, Kenific C, Kunii K, Leach KJ, Nikov G, Zhao J, Dai X, Hardwick J, Scott M, Winter C, Bristow L, Elbi C, Reilly JF, Look T, Draetta G, Van der Ploeg L, Kohl NE, Strack PR, Majumder PK (2009) Down-regulation of the Notch pathway mediated by a gamma-secretase inhibitor induces anti-tumour effects in mouse models of T-cell leukaemia. Br J Pharmacol 158:1183–1195PubMedCrossRef Tammam J, Ware C, Efferson C, O’Neil J, Rao S, Qu X, Gorenstein J, Angagaw M, Kim H, Kenific C, Kunii K, Leach KJ, Nikov G, Zhao J, Dai X, Hardwick J, Scott M, Winter C, Bristow L, Elbi C, Reilly JF, Look T, Draetta G, Van der Ploeg L, Kohl NE, Strack PR, Majumder PK (2009) Down-regulation of the Notch pathway mediated by a gamma-secretase inhibitor induces anti-tumour effects in mouse models of T-cell leukaemia. Br J Pharmacol 158:1183–1195PubMedCrossRef
37.
Zurück zum Zitat Efferson CL, Winkelmann CT, Ware C, Sullivan T, Giampaoli S, Tammam J, Patel S, Mesiti G, Reilly JF, Gibson RE, Buser C, Yeatman T, Coppola D, Winter C, Clark EA, Draetta GF, Strack PR, Majumder PK (2010) Downregulation of Notch pathway by a gamma-secretase inhibitor attenuates AKT/mammalian target of rapamycin signaling and glucose uptake in an ERBB2 transgenic breast cancer model. Cancer Res 70:2476–2484PubMedCrossRef Efferson CL, Winkelmann CT, Ware C, Sullivan T, Giampaoli S, Tammam J, Patel S, Mesiti G, Reilly JF, Gibson RE, Buser C, Yeatman T, Coppola D, Winter C, Clark EA, Draetta GF, Strack PR, Majumder PK (2010) Downregulation of Notch pathway by a gamma-secretase inhibitor attenuates AKT/mammalian target of rapamycin signaling and glucose uptake in an ERBB2 transgenic breast cancer model. Cancer Res 70:2476–2484PubMedCrossRef
Metadaten
Titel
DAPT protects brain against cerebral ischemia by down-regulating the expression of Notch 1 and Nuclear factor kappa B in rats
verfasst von
Shuya Li
Xiangjian Zhang
Yongjun Wang
Hui Ji
Yuanyuan Du
Haichao Liu
Publikationsdatum
01.12.2012
Verlag
Springer Milan
Erschienen in
Neurological Sciences / Ausgabe 6/2012
Print ISSN: 1590-1874
Elektronische ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-012-0948-6

Weitere Artikel der Ausgabe 6/2012

Neurological Sciences 6/2012 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Thrombektomie auch bei großen Infarkten von Vorteil

16.05.2024 Ischämischer Schlaganfall Nachrichten

Auch ein sehr ausgedehnter ischämischer Schlaganfall scheint an sich kein Grund zu sein, von einer mechanischen Thrombektomie abzusehen. Dafür spricht die LASTE-Studie, an der Patienten und Patientinnen mit einem ASPECTS von maximal 5 beteiligt waren.

Schwindelursache: Massagepistole lässt Otholiten tanzen

14.05.2024 Benigner Lagerungsschwindel Nachrichten

Wenn jüngere Menschen über ständig rezidivierenden Lagerungsschwindel klagen, könnte eine Massagepistole der Auslöser sein. In JAMA Otolaryngology warnt ein Team vor der Anwendung hochpotenter Geräte im Bereich des Nackens.

Schützt Olivenöl vor dem Tod durch Demenz?

10.05.2024 Morbus Alzheimer Nachrichten

Konsumieren Menschen täglich 7 Gramm Olivenöl, ist ihr Risiko, an einer Demenz zu sterben, um mehr als ein Viertel reduziert – und dies weitgehend unabhängig von ihrer sonstigen Ernährung. Dafür sprechen Auswertungen zweier großer US-Studien.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.