γ-Secretase modulators do not induce Aβ-rebound and accumulation of β-C-terminal fragment (pages 277–286)
Ting Li, Yunhong Huang, Shiyi Jin, Liang Ye, Na Rong, Xiujuan Yang, Yu Ding, Ziqiang Cheng, Jinqiang Zhang, Zehong Wan, David C. Harrison, Ishrut Hussain, Adrian Hall, Daniel Hong Seng Lee, Lit-Fui Lau and Yasuji Matsuoka
Version of Record online: 13 MAR 2012 | DOI: 10.1111/j.1471-4159.2011.07560.x
γ-secretase modulators avoid paradoxical Aβ rebound and accumulation of β-C-terminal fragment caused by γ-secretase inhibitors. A γ-secretase inhibitor, LY-450139, designed to slow cognitive decline in Alzheimer’s patients ended up doing the opposite in a phase III trial. LY-450139 is known to cause paradoxical Aβ rebound, the significance of which in the adverse effects remains to be determined. γ-Secretase modulators can reduce Aβ 40 and 42 without triggering Aβ rebound and β-CTF accumulation. They might be a better alternative in treating Alzheimer’s disease.