Oxidative stress mediates tau-induced neurodegeneration in Drosophila
J. Clin. Invest. Dora Dias-Santagata, et al. 117:236 doi:10.1172/JCI28769 [Go to this article.]

Figure 5
Oxidative stress does not act by altering tau phosphorylation. (A) Increased oxidative stress did not clearly modify tau phosphorylation. Equivalent amounts of fly head extracts (day 10) were analyzed by Western immunoblotting using the indicated antibodies. Genotypes for each column are as follows: control, elav-GAL4/+; tau^R406W, elav-GAL4/+, UAS-tau^R406W/+; tau^R406W + Trxr^Δ1, elav-GAL4/Trxr^Δ1, UAS-tau^R406W/+; and tau^R406W + Sod2ⁿ²⁸³, elav-GAL4/+, Sod2ⁿ²⁸³/+, UAS-tau^R406W/+. (B) Genetic downregulation of antioxidant enzymes enhanced neurotoxicity in transgenic flies expressing a pseudophosphorylated mutant form of tau. Compared with that in flies expressing tau^E14, neurodegeneration was significantly increased in tau^E14 transgenic animals heterozygous for Trxr^Δ1 (**P < 0.01) or for Sod2ⁿ²⁸³ (**P < 0.01). Quantification of TUNEL-positive cells in the brains of 5-day-old transgenic flies was used to evaluate neurotoxicity levels in transgenic animals. Genotypes are as follows: control, elav-GAL4/+, UAS-tau^WT/+; tau^E14, elav-GAL4/+, UAS-tau^E14(22)/+; tau^E14 + Trxr^Δ1, elav-GAL4/Trxr^Δ1, UAS-tau^E14(22)/+; and tau^E14 + Sod2ⁿ²⁸³, elav-GAL4/+, Sod2ⁿ²⁸³/+, UAS-tau^E14(22)/+.