2.1.6. TRPA1 Activation by microRNA in the Central Nervous System

Although TRPA1 is expressed in both brain and spinal cord cells, whether it is activated via direct or indirect pathways is unclear. In the central nervous system, only one obvious possibility exists for direct activation of TRPA1 by an endogenous ligand, namely microRNA (miRNA). Among the miRNAs present in cerebrospinal fluid, increased levels of let-7b are particularly associated with the incidence of Alzheimer's disease. Meanwhile, astrocytes can exacerbate symptoms associated with amyloid-induced TRPA1 activation [69,70]. Let-7b activates TLR7, which is followed by cytotoxicity and direct activation of TRPA1 [71]. Importantly, let-7b release is enhanced by formalin application to DRG, while let-7b injection induces both nociceptive behavior and mechanical allodynia, which are reduced in TRPA1- and TLR7-deficient mice. These results demonstrate a relationship between let-7b and TRPA1 as a possible molecular mechanism of inflammatory symptoms in central nervous system diseases.
