Figure 5. The APP amino terminus regulates degeneration.
(a) Local degeneration of sensory axons in Campenot chambers (NGF deprivation, 24hr) was blocked by anti-N-APP(poly) (20 ug/ml). Quantification in (a′).
(b) In dissociated sensory neurons, siRNA knock-down of APP significantly reduces axon degeneration 24hr after trophic deprivation, and partially reduces cell body death. Quantification in (b′).
(c)Local degeneration of sensory axons in Campenot chambers (NGF deprivation, 24hr) was inhibited by local addition of BACE inhibitor OM99-2 (10μM). Purified APP[1–286] added locally restored axonal degeneration, an effect inhibited by 50 ng/ml NGF (right). Quantification in (c′).
(d)Degeneration of commissural neurons and axons at 48hr was inhibited by anti-N-APP(poly) (20 ug/ml) or BACE inhibitor OM99-2 (10μM), but restored by APP[1–286]. Quantification in (d′).
(e) Effect of Abeta antibodies on sensory axon degeneration (NGF deprivation, 24hr). 4G8 partially inhibited; anti- Abeta[17–24] did not. Quantification in (e′).
Scale bar: (a, c, e): 50 μm; (b): 40 μm; (d): 200 μm.