Semaphorin3A-PlexinA シグナルによるアミロイドβ前駆タンパク質の機能及び代謝制御

抄録

The amyloid-beta peptide (Aβ), a major component of senile plaques, is believed to be the underlying trigger of the development of Alzheimer's disease (AD). The elucidation of mechanism(s) that induce Aβ overproduction from its type I transmembrane precursor protein (APP) is therefore important for the development of effective AD therapies. Semaphorin3A (Sema3A), a secreted type of repulsive axon guidance molecule, is implicated in the development of various neurodegenerative diseases. It was reported that Sema3A and its signaling molecules accumulated and aggregated in the brain of AD patients. However, the molecular link between Sema3A signaling and AD pathogenesis remains unknown. Here, we provide evidence regarding the interaction between APP and PlexinA, a Sema3A receptor component, through their extracellular regions. We also narrowed down the interacting regions to 100 amino acid or less. Based on these findings, we are now investigating whether the APP-PlexinA interaction affects APP function and metabolism, which might provide novel insights into involvement of Sema3A signaling in overproduction of Aβ.