A presenilin 1 mutation associated with familial frontotemporal dementia inhibits γ-secretase cleavage of APP and notch
Neurobiology of disease, 2002•Elsevier
A novel presenilin 1 mutation, insR352, associated with a frontal temporal dementia
phenotype has been identified (EA 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 phenotype associated with this mutation suggests that chronic
partial inhibition of γ-secretase activity may result in neurodegeneration.
phenotype has been identified (EA 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 phenotype associated with this mutation suggests that chronic
partial inhibition of γ-secretase activity may result in neurodegeneration.
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 phenotype associated with this mutation suggests that chronic partial inhibition of γ-secretase activity may result in neurodegeneration.
Elsevier