Downregulation of AKT-mediated p27^Kip1 phosphorylation with shift to sphingomyelin synthesis in CLN3 disease.

ABSTRACT: CLN3 disease is a fatal childhood neurodegenerative disorder without drug-modifying therapies. Wild-type CLN3 gene is anti-apoptotic. Previous work proves that CLN3 disease pathogenesis is associated with reduced cell viability/apoptotic cell death and increase in ceramide, in cells and brains of patients and in Cln3 ^Δex7/8 mouse brain. AKT, a serine/threonine protein kinase, is at the core of a complex signaling pathway regulating apoptosis and cell proliferation and is neuroprotective. AKT fulfils this function via cyclin-dependent kinase inhibitor p27^Kip1 phosphorylation at residue T198 resulting in its cytoplasmic localization and promotion of cell survival. Transcriptomic analysis of gene expression using microarrays, validation by Western bl

SUBMITTER: Bilal F 

PROVIDER: S-EPMC12270666 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature