APP for injury repair

The cleavage of the amyloid precursor protein (APP) by γ-secretase releases the Aβ peptide, which forms plaques that are associated with Alzheimer's. Because APP is induced by injury, boxers and head trauma sufferers are prone to developing Alzheimer's. But new findings suggest that, without APP, the initial injuries might be lethal. Maarten Leyssen, Bassem Hassan, and colleagues (VIB and the University of Leuven, Belgium) find that APP helps mature axons grow and branch.

The function of APP has been elusive, as mice and flies lacking APP develop relatively normally. So to look for postdevelopmental functions, Hassan's group induced neuronal APP expression in adult flies. The result was a strong arborization of mature axons.Recalling that APP is induced by injury, Leyssen devised a strategy to produce head wounds in flies. “The APP mutants,” says Hassan, “had a lower chance of survival after their injuries.” Survival probably depends on restoring severed synaptic connections, which would be helped along by axonal arborization.

APP works by activating Abl, a kinase that destabilizes actin filaments. The authors find that the JNK pathway is also activated by injury and is required for APP-induced arborization. Although the Abl pathway probably produces immediate responses needed for axon outgrowth, JNK-induced transcriptional changes might be longer lasting, perhaps even returning the mature neuron to growth mode.

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