Glutamate metabolism disruption in Johanson-Blizzard syndrome: Insights from C. elegans ubr-1 model.

Abstract

The Johanson-Blizzard syndrome (JBS) is a complex autosomal recessive disorder that manifests through a spectrum of symptoms, with deficiencies in the ubiquitin-protein ligase E3 component N-recognin 1 (UBR-1) at its genetic core. Despite its clinical significance, the molecular intricacies of UBR-1's role in JBS remain largely elusive, presenting a formidable challenge in devising targeted treatments. The nematode Caenorhabditis elegans, with its genetic tractability and conservation of fundamental biological mechanisms, emerges as an invaluable model for unravelling the molecular underpinnings of JBS. This review integrates the latest discoveries from C. elegans studies, shedding light on UBR-1's multiple functions: its regulatory impact on cellular pathways and, particularly, its crucial involvement in glutamate metabolism. By assessing the contributions of these studies to our understanding of JBS, this review highlights the potential significance of glutamate metabolic dysfunction in JBS pathogenesis.