Nebula/DSCR1 Upregulation Delays Neurodegeneration and Protects against APP-Induced Axonal Transport Defects by Restoring Calcineurin and GSK-3β Signaling
Figure 1
Nebula overexpression reduces APP-induced degeneration structurally and functionally.
(A) Cryostat section of 15-day old flies. Neurodegeneration is seen as holes in the fly retina (arrow). Photoreceptor neurons were detected with mAb24B10 (red) and N-APP antibody (green). To normalize the number of transgenes found in different fly lines, control, APP overexpression (OE), or APP;nla1 flies also carry one copy of UAS-LacZ gene driven by Gmr-GAL4. (B) Fold change in % area lost. n>4 heads per genotype and age. (C) Percentage of flies that moved toward light. n = 3–4 separate tests, total >100 flies per genotype. All values are mean ± S.E.M, * p≤0.05 compared to control, ** P<0.05 compared to the indicated genotypes. (D) Sections of 45 day old fly heads stained with mAb6E10 (APP) and with antibody specific for pT668-APP. White arrow highlights vacuoles and yellow arrowhead points to aggregates. The medulla in which R7-8 terminate is magnified on the right. More pT668-APP is seen in the axon terminals of the photoreceptor neurons (highlighted by magenta arrow).