Consequences of Inhibiting Amyloid Precursor Protein Processing Enzymes on Synaptic Function and Plasticity

Figure 4

The roles of presenilins in synaptic function. Two main functions of presenilin 1 (PS1) focused on in this paper are its ability to function as part of the γ-secretase cleavage complex and also to function as an ER Ca²⁺ leak channel. The γ-secretase complex is responsible for the final cleavage of APP in the production of Aβ peptides. The γ-secretase complex has also been shown to regulate spontaneous neurotransmitter release and is crucial for the regulation of the notch signaling pathway especially during early development. The PS1 holoprotein has been proposed to function as an ER Ca²⁺ leak channel. It is responsible for regulating intracellular calcium dynamics and calcium homeostasis required for proper signaling and neurotransmitter release. In addition to these two main functions, knockout studies have shown that the PS1 protein is important for synaptic scaling, proper NMDAR-mediated responses, as well as cell adhesion mediated by N-cadherin. Through these studies it is clear that PS1 plays an important role in synaptic transmission and plasticity.