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Presenilins (PSs) are the catalytic core of γ-secretase complex. However, the mechanism of FAD-associated PS mutations in AD pathogenesis still remains elusive. Here we review the general biology and mechanism of γ-secretase and focus on the catalytic components - presenilins and their biological functions and contributions to the AD pathogenesis. The functions of presenilins are divided into γ-secretase dependent and γ-secretase independent ones. The γ-secretase dependent functions of presenilins are exemplified by the sequential cleavages in the processing of APP and Notch; the γ-secretase independent functions of presenilins include stabilizing β-catenin in Wnt signaling pathway, regulating calcium homeostasis and their interaction with synaptic transmission.
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Zhang et al. (2013) studied this question.
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