Loss of UBE3A drives Angelman syndrome through persistent neuronal stress signalling

A study published in Nature on 21 October 2026 traces a mechanistic chain behind Angelman syndrome. Genetic and proteomic analyses of human neurons and mouse models show that loss of the UBE3A gene leads to excess asparagine synthetase, and that this surplus is linked to multiple Angelman syndrome phenotypes. The researchers connect the chain to persistent neuronal stress signalling in neurons, proposing it as an underlying basis of the disorder's features. The findings come from laboratory models and human neuronal cells, so the mechanism now awaits testing in patients. Open questions include whether the asparagine synthetase pathway can be targeted therapeutically and how the stress signalling relates to other proposed mechanisms of the syndrome.

Written by a model from the reports · updated 3 hours ago