These findings are of particular interest because treatment of zebrafish models of Frontotemporal Dementia and Huntington’s disease with the PDE5 or the PDE4 inhibitors not only promoted the selective degradation of the disease-associated hyperphosphorylated tau mutants (A152T and P301L), as well as huntingtin containing a 71-polyQ sequence, but both treatments also reduced the associated neuronal death and the marked developmental abnormalities seen upon expression of these mutant proteins (Figure 8). The gene discussed is MAPT; the disease is juvenile Huntington disease.