Aβ42 induced rough eye phenotype is sensitive to <i>Toll</i> activity.

<p>WT: Wild type flies. Aβ: pGMR-Aβ42 transgenic flies. In the experiments shown in this figure, the flies are hemizygous for the pGMR-Aβ42 transgene. Panel A: WT: eye of a wild type fly. Aβ/+: eye of a wild type fly hemizygous for the pGMR-Aβ42 transgene. Panels B through F show sibling pGMR-Aβ42 transgene flies that are either wild type <i>Tl</i> or heterozygous for the indicated <i>Tl</i> allele. Panel B: Aβ/+: hemizygous for the Aβ transgene; Aβ/<i>Tl^r4</i>: heterozygous for the LOF allele <i>Tl^r4</i>. Panel C: Aβ/+: hemizygous for the Aβ transgene; Aβ/<i>Tl^r3</i>: heterozygous for the LOF allele <i>Tl^r4</i>. Panel D: Aβ/+: hemizygous for the Aβ transgene; Aβ/<i>Tl^KG</i>: heterozygous for the LOF allele <i>Tl^KG03609</i>. Panel E: Aβ/+: hemizygous for the Aβ transgene; Aβ/<i>Tl^rk</i>: heterozygous for the LOF allele <i>Tl^rK343</i>. Panel F: Aβ/+: hemizygous for the Aβ transgene; Aβ/<i>Tl³</i>: heterozygous for the GOF allele <i>Tl^r3</i>.</p

The <i>Drosophila</i> Toll→Dorsal/Dif and mammalian Interleukin Receptor→NFκB innate immunity pathways.

<p>Diagram of the <i>Tl</i>→NFκB signaling pathways in <i>Drosophila</i> and mammals. See text for details.</p

Dorsal mediates Aβ42 dependent neurodegeneration of the eye.

<p>Panels A–E: In the experiments shown in this figure all flies are siblings that are homozygous for the pGMR-Aβ42 transgene. The fly on the left side of each panel is a wild type sib, while the fly on the right side of each panel is a sib that is either heterozygous or homozygous for the indicated <i>dl</i> mutation. Panel A: <i>dl¹</i>/+. Panel B: <i>dl⁴</i>/+ Panel C: <i>dl⁸</i>/+ Panel D: <i>dl¹</i>/<i>dl¹</i>. Panel E: <i>dl⁴/dl⁴</i>. Panel F: In this experiment both flies are hemizygous for the pGMR-Aβ42 transgene. The fly on the left is wild type, while the fly on the right is homozygous <i>dl^`</i>. Arrows in panels A and E point to ommatidia with dead or dying cells.</p

Effect of mutations in the <i>Tl→ΝFκB</i> pathway on the Aβ42 induced rough eye phenotype.

<p>The rough eye phenotype of pGMR-Aβ42 flies was assigned a value of ++++. According to this scoring system, strong, moderate and weak suppression corresponded to +, ++, and +++. Weak and moderate enhancement corresponded to +++++ and ++++++. All flies are hemizygous for the transgene and either wild type (+) or heterozygous for the indicated mutation.</p

Components of the <i>Toll-NF</i>κ<i>B</i> signaling pathway modulate Aβ42 polypetide induced neurodegeneration.

<p>Panels A–F: In the experiments shown in this figure all flies are siblings that are hemizygous for the pGMR-Aβ42 transgene. The fly on the left side of each panel is a wild type sib, while the fly on the right side of each panel is a sib that is heterozygous for the indicated mutation in the <i>Toll-NF</i>κ<i>B</i> signaling pathway mutant. Panel A: <i>dl¹</i>. Panel B: <i>dl⁴</i>. Panel C: <i>dl⁸</i>. Panel D: <i>pll²</i>. Panel E: <i>pll⁷</i>. Panel F: <i>tub</i>.</p