Figure 2.

Hypothetical model of cotinine's potentiation of the α7 nAChR. The scheme represents the hypothetical positive allosteric modulation of the α7 nAChR by cotinine, and the activation of signaling pathways that are downstream of the a7 nAChR. The consequences of the activation by cotinine of components of the PI3K‐Akt‐GSK3β pathway on AD pathology are suggested. The activation of Akt by cotinine may result in the inhibition of the tau kinase GSK3β and consequently the formation of hyperphosphorylated forms of tau found in the neurofibrillary tangles (one of the neuropathological hallmarks of AD). Also, the inhibition of GSK3β may inhibit its pro‐apoptotic effect. On the other hand, the stimulation of pERK can stimulate pCREB activity and as a result stimulate the expression of Arc, a protein that participate in the remodeling of the synapses during learning and memory processes and is required for long‐term memory. CREB stimulate the expression of antiapoptotic factors such as Bcl2.