UN2CpolyG-mediated p65 nuclear sequestration suppresses the NF-κB-NLRP3 pathway in neuronal intranuclear inclusion disease.

ABSTRACT:

Background

Neuronal intranuclear inclusion disease (NIID) is genetically linked to CGG repeat expansion in the 5'-untranslated region of the NOTCH2NLC gene, with nascent polyglycine-containing protein (uN2CpolyG) identified as a primary pathogenic factor. Emerging clinical evidence suggests that inflammation contributes to NIID pathogenesis, yet the underlying molecular mechanisms remain elusive. This study aimed to elucidate the molecular interaction between uN2CpolyG and the NF-κB-NLRP3 pathway.

Methods

Single-cell RNA sequencing was conducted on the skin tissues of NIID patients to assess changes in the expression of genes involved in inflammatory pathways. Cell models (HEK-293T and U87-MG) transfected with CGG_9/69/100 expansion vectors were used to investigate

SUBMITTER: Shen Y 

PROVIDER: S-EPMC11806584 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature