Fig. 7

Schematic diagram showing the mechanisms of tau-induced autophagy dysfunction. The molecular mechanisms involve a direct binding of N-terminal tau to the TIA1-PRD to detain TIA1 in the cytoplasm, by which TIA1 is detained in the cytoplasm to form SGs, leading to the inhibition of protein synthesis, increases of intracellular AA concentration, mTORC1 activation, autophagosome reduction and finally autophagy deficit. The autophagy deficit in turn aggravates tau accumulation during chronic neurodegeneration, as observed in AD and related tauopathies. AA amino acid, AD Alzheimer’s disease, mTORC1 the mammalian target of rapamycin kinase complex 1, SGs stress granules, TIA1 T cell intracellular antigen 1, PRD the prion-related domain