Figure 1.

Schematic representation of PS-dependent processing of substrates and their role in synaptic function. Several γ-secretase substrates are located at the synapse where they influence the function of other synaptic proteins. Lack of γ-secretase-dependent cleavage of substrates could perturb presynaptic release and postsynaptic function of glutamate receptor-mediated events (NMDA-GluN and AMPA-GluA receptors). Synaptic contact could also be modulated through cell-adhesion properties of several γ-secretase substrates. Inefficient processing of these substrates will lead to sustained activation of signaling cascades capable of altering the postsynaptic morphology. How FAD-linked mutations in PS influence these processes and contribute to the disease progression has not been fully understood.