Semaphorin3A-PlexinAシグナルがアミロイドβ前駆タンパク質の機能や代謝に与える影響

抄録

Amyloid-beta (Aβ) aggregation has been believed to be the fundamental trigger of the development of Alzheimer's disease (AD). Therefore, elucidating the mechanisms that induce Aβ overproduction from its type I transmembrane precursor protein (APP) is one of the important issues in providing potential therapeutic targets for AD. Semaphorin3A (Sema3A), a secreted type of repulsive axon guidance molecule, is implicated in the development of various neurodegenerative diseases. It was previously reported that Sema3A and its signaling molecules accumulate and aggregate in AD patients' brain. However, the molecular link between Sema3A signaling and AD pathogenesis remains unknown. Here we show evidence that APP interacts with PlexinA, a Sema3A receptor component. APP and PlexinA interacted through the extracellular regions and we were able to narrow down these regions to less than 100 amino acids. Based on these findings, we are now investigating whether the APP-PlexinA interaction affects APP function and metabolism, which might provide new perspective that aberrant Sema3A signaling induces Aβ overproduction.