Alpha 7 nicotinic acetylcholine receptor and its effects on Alzheimer's disease

Alzheimer's disease (AD) is one of the major disabling and lethal diseases for aged individuals worldwide. To date, there are more than 10 hypotheses proposed for AD pathology. The beta-amyloid (Aβ) cascade hypothesis is the most widely accepted and proposes that the accumulation of Aβ in the brain is one potential mechanism for AD pathogenesis. Because some Aβ-overloaded patients do not have AD syndrome, this hypothesis is challenged from time to time. More recently, it has been shown that intracellular Aβ plays a key role in AD pathology. Aβ is internalized by receptors distributed on the cell membrane. Among these receptors, the alpha7 nicotinic acetylcholine receptor (α7 nAChR) has been shown to play an important role in AD. The α7 nAChR is a ligand-gated ion channel and is expressed in pivotal brain regions (e.g., the cerebral cortex and hippocampus) responsible for cognitive functions. The α7 nAChR is localized both presynaptically and postsynaptically, where it activates intracellular signaling cascades. Its agonist has been investigated in clinical studies to improve cognitive functions in AD. Although many studies have shown the importance of the α7 nAChR in AD, little is known regarding its role in AD pathology. Therefore, in the current review, we summarized the basic information regarding the structures and functions of the α7 nAChR, the distribution and expression of the α7 nAChR, and the role of the α7 nAChR in mediating Aβ internalization. We subsequently focused on introducing the comprehensive α7 nAChR related signaling pathways and how these signaling pathways are integrated with the α7 nAChR to play a role in AD. Finally, we stressed the AD therapy that targets the α7 nAChR.