Fig. 1.

Role of TRP channels in Alzheimer's disease. Aβ-peptide stimulates the TRPA1 and enhances the ROS generation, which destabilizes the intracellular Ca2+ homeostasis, and initiation of IP3R initiates ER Ca2+ store depletion, resulting in the elevation of cytoplasmic Ca2+ which increases the expression of PP2B and NFкB. Generation of ROS, released in the cytosol, can trigger TRPM2 and a subsequent increase in intracellular Ca2+ ions induce NO production. Activated astrocytes and microglial cells by Aβ promotes TNFα, activating TRPM2 and NO, which stimulates TRPC5 and mediates Ca2+-dependent NO production by neuronal NOS. Aβ triggers the activation of neuroinflammatory processes, directed by activated-glial cells that produce inflammatory cytokines, which activate TRPV1. All these events cause neuronal death and eventually lead to the pathogenesis of AD.