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Genes Environment Amyloid cascade hypothesis – the role of GSK3 AT8 GSK-3 inhibitor GSK3 1. Hanger et al. Neurosci.Lett. 1992;147:58-62. 2. Lovestone et.

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Presentation on theme: "Genes Environment Amyloid cascade hypothesis – the role of GSK3 AT8 GSK-3 inhibitor GSK3 1. Hanger et al. Neurosci.Lett. 1992;147:58-62. 2. Lovestone et."— Presentation transcript:

1 Genes Environment Amyloid cascade hypothesis – the role of GSK3 AT8 GSK-3 inhibitor GSK3 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.

2 Animal models – GSK3 as the memory molecule Mudher et al (2004) 9, 522 530 Phenotype GSK3 inhibited Tet/GSK3 70 80 90 100 110 120 130 140 150 160 170 -30-20-100102030405060708090100110120 Time (mins) Amplitude EPSP (% baseline) wt Hooper et al Eur J Neurosci (2007); 25: 81-86. GSK3 inhibitor

3 The GSK3 cascade and drug discovery for Alzheimers GSK3 inhibitors in phase IIb trials Drug discovery programme – DKK1 and the cascade Companion biomarkers Dkk1GSK3Dkk1


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