Whereas Tau is predominantly localized in neuronal axon and involved in microtubule stability, Tau dissociates from microtubules and forms aggregates in pathological conditions such as Alzheimer’s disease and frontotemporal dementia. These neurodegenerative diseases are called tauopathies, however, the mechanism underlying formation of Tau aggregates remain uncertain. We have previously reported that RNA G-quadruplexes (G4) is a key factor to induce Tau aggregation in vitro. Here, we would like to propose the mechanism underlying neurodegeneration by G4-induced Tau aggregation in neuronal axon and then the novel therapeutics for tauopathies targeting G4.