A novel OTUD5 variant disrupts neural progenitor cell homeostasis: mechanistic insights from HEK293T cell-based analyses - PubMed
5 hours ago
- #Neurodevelopmental Disorders
- #GSK3β
- #OTUD5
- A novel OTUD5 variant (c.697G > A, p.Val233Met) is linked to neurodevelopmental disorders (NDDs).
- The variant disrupts neural progenitor cell (NPC) homeostasis, leading to aberrant proliferation and impaired neuronal differentiation.
- Mechanistically, the variant reduces OTUD5's deubiquitinase activity, destabilizing GSK3β and shortening its half-life by 40%.
- Patient-derived iPSCs and CRISPR/Cas9-corrected isogenic controls were used to study the variant's effects.
- The study highlights the role of ubiquitination regulation in neurodevelopment and suggests potential GSK3β-targeted therapies for OTUD5-related NDDs.