Figure 6.

Annonacin-induced complex I inhibition is responsible for the somatic redistribution of tau. A, Immunohistochemistry with an antibody against yeast NDI1 shows the efficient rAAV-mediated expression of this protein (green, arrows) in transfected cells. As expected, no immunoreactivity for the yeast protein was detected in untransfected control cells. NDI1 is able to replace the NADH-oxidizing function of complex I in mammalian cells (Seo et al., 2002). DAPI (blue) stains nuclei. B–D, ATP levels (B), cell death (C), and somatic redistribution of AD2⁺ tau (D) in control (Cont) cultures of striatal neurons and in cultures exposed to 100 nm annonacin (Anno; 6 h for ATP, 48 h for survival and AD2), in the absence or the presence of NDI1 expression. *p < 0.05, ***p < 0.001 versus control; ^#p < 0.05, ^###p < 0.001 versus annonacin alone. E, Photomicrographs showing that NDI1 expression prevents the annonacin-induced cell death and somatic redistribution of AD2⁺ tau (red, arrow) in cultured striatal neurons. DAPI (blue) stains nuclei. Scale bars: A, E, 10 μm.