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Amyloid cascade hypothesis – the role of GSK3

Amyloid cascade hypothesis – the role of GSK3. Environment. Genes. GSK3. AT8. 1. Hanger et al. Neurosci.Lett. 1992;147:58-62. 2. Lovestone et al Curr Biol 1994;4(12):1077-86. 3. Lovestone et al Biol.Psychiatry 1999;45(8):995-1003. GSK-3 inhibitor.

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Amyloid cascade hypothesis – the role of GSK3

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  1. Amyloid cascade hypothesis – the role of GSK3 Environment Genes GSK3 AT8 1. Hanger et al. Neurosci.Lett. 1992;147:58-62. 2. Lovestone et al Curr Biol 1994;4(12):1077-86. 3. Lovestone et al Biol.Psychiatry 1999;45(8):995-1003. GSK-3 inhibitor

  2. Animal models – GSK3 as the memory molecule 170 160 Phenotype Tet/GSK3 150 wt 140 130 GSK3 inhibited Amplitude EPSP (% baseline) 120 110 100 90 80 70 -30 -20 -10 0 10 20 30 40 50 60 70 80 90 100 110 120 Time (mins) GSK3 inhibitor Mudher et al (2004) 9, 522-530 Hooper et al Eur J Neurosci (2007); 25: 81-86.

  3. The GSK3 cascade and drug discovery for Alzheimer’s Dkk1 • GSK3 inhibitors in phase IIb trials • Drug discovery programme – DKK1 and the cascade • Companion biomarkers Dkk1 GSK3

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