Proteasomal activation ameliorates neuronal phenotypes linked to FBXO11-deficiency.

ABSTRACT: Haploinsufficiency of FBXO11, encoding a ubiquitin ligase complex subunit, is associated with a variable neurodevelopmental disorder. So far, the underlying nervous system-related pathomechanisms are poorly understood, and specific therapies are lacking. Using a combined approach, we established an FBXO11-deficient human stem cell-based neuronal model using CRISPR-Cas9 and a Drosophila model using tissue-specific knockdown techniques. We performed transcriptomic analyses on iPSC-derived neurons and molecular phenotyping in both models. RNA sequencing revealed disrupted transcriptional networks related to processes important for neuronal development, such as differentiation, migration, and cell signaling. Consistently, we found that loss of FBXO11 leads to neuronal phenotypes such as impair

SUBMITTER: Gregor A 

PROVIDER: S-EPMC11999343 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature