Post on 28-Mar-2015
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.
Animal models – GSK3 as the memory molecule
Mudher et al(2004) 9, 522530
Phen
otyp
e
GSK3 inhibited
Tet/GSK3
708090
100110120130140150160170
-30-20-10 0 10 20 30 40 50 60 70 80 90 100110120Time (mins)
Ampl
itude
EPS
P (%
bas
elin
e)
wt
Hooper et al Eur J Neurosci (2007); 25: 81-86.
GSK3 inhibitor
The GSK3 cascade and drug discovery for Alzheimer’s
• GSK3 inhibitors in phase IIb trials
• Drug discovery programme – DKK1 and the cascade
• Companion biomarkers
Dkk1 GSK3Dkk1