Figure 13. Activation of α7 nAChR by PNU-282987 improves synaptic and cognitive functions through restoring the expression of synaptic-associated proteins and the CaM-CaMKII-CREB signaling pathway. Synapses are the basic structure for the connection between neurons, and the function of a synapse is largely associated with synaptic-associated proteins. The present study found that activation of α7 nAChRs by PNU-282987 could largely restore the expression level of synaptic-associated proteins, including SYN, PSD95, SNAP25, DYN1 and AP180, which are downregulated by deposition of Aβ. α7 nAChRs belong to the ligand-gated ion channel coupled receptors, and form an ion channel in the center, which mainly regulates the flow of Ca2+ plasma inside and outside the cell. As a second cytoplasmic messenger, Ca2+ can flow into the cells through α7 nAChRs and bind to CaM to form an active CaM complex. The CaM complex can bind to CaMKII, which changes the CaMKII spatial conformation and phosphorylates CaMKII protein. Phosphorylated CaMKII enters the nucleus to catalyze CREB phosphorylation. CREB is located downstream of the α7 nAChR signal transduction pathway and acts as a transcription factor that regulates the growth and development of neurons and the formation of long-term memory.