Back to article: Making the final cut: pathogenic amyloid-β peptide generation by γ-secretase


FIGURE 8: Pseudoinhibiton of γ-secretase by semagacestat. Cleavage of C99 by γ-secretase causes the generation of secreted and intracellular Aβ pools as well as γ-byproducts from carboxy-terminal trimming of the C99 TMD. Unlike TSA-GSIs such as L-685,458, semagacestat causes an intracellular accumulation of long Aβ species and byproducts demonstrating a pseudo-inhibition of γ-secretase by this and related compounds.

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