A Presenilin 1 Mutation Associated with Familial Frontotemporal Dementia Inhibits γ-Secretase Cleavage of APP and Notch
作者： Zareen Amtul , Patrick A. Lewis , Sian Piper , Richard Crook , Matt Baker
关键词: Neurodegeneration 、 Presenilin 1 mutation 、 Phenotype 、 Molecular biology 、 Genetics 、 Presenilin 、 Chemistry 、 Neurology 、 Cleavage (embryo) 、 Frontotemporal dementia 、 Dementia
摘要: Abstract A novel presenilin 1 mutation, insR352, associated with a frontal temporal dementia phenotype has been identified (E. A. Rogaeva et al., 2001, Neurology 57, 621–625). This mutation does not increase Aβ42 levels, but instead acts as dominant negative presenilin, decreasing amyloid β protein (Aβ) production by inhibiting γ-secretase cleavage of the Aβ precursor. The distinct clinical this suggests that chronic partial inhibition activity may result in neurodegeneration.
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