08:18am Monday 21 October 2019

Alzheimer’s-disease-related proteases, BACE1 and APH1B-y-secretase, control axonal guidance by regulating growth cone dynamics

Soraia Barão (VIB/KU Leuven): “We reveal a cycle of proteolytic activity underlying growth cone collapse and restoration used by axons to find their correct trajectory in the brain. Our data show that BACE1 and y-secretase inhibition have physiologically opposite effects in this process, suggesting that cautiously-designed combination therapies might attenuate some of the side effects associated with these drugs.”

Bart De Strooper (VIB/KU Leuven): “Based on this new knowledge of the functions of both proteases (BACE1 cleaves CHL1, inducing growth cone collapse. Subsequently, y-secretase activity stops the collapse and axonal growth resumes.), we think it wise to proceed the testing of inhibitors of these proteases in humans with caution.”

Antagonistic Effects of BACE1 and APH1B-y-Secretase Control Axonal Guidance by Regulating Growth Cone Collapse, Barão et al., Cell Reports 2015


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