Potential role of miRNAs in tau metabolism regulation. (a, b) Two models are shown demonstrating how specific miRNAs could be involved in the regulation of tau phosphorylation (and aggregation) and/or tau exon 10 alternative splicing. Note that some miRNAs are affected in disease conditions (in green, downregulated in AD; in red, downregulated in PSP). Whether other miRNA target effectors are involved in the physiological and/or pathological regulation of tau metabolism remains to be explored. Any changes in the level or function of these miRNAs could have serious biological consequences, including tau hyperphosphorylation and aggregation and an imbalance in tau microtubule-binding repeats (encoded in tau exon 10, giving rise to either four 4R-tau or 3R-tau). Regulation of tau exon 10 splicing by PTBP1 or PTBP2 may be direct or may implicate other coregulators such as TDP-43 or PSF, both of which have been shown to either regulate PTBP2 expression or regulate PTBP splicing and repress tau exon 10 inclusion [26, 52–54].
