Opposing roles for GSK3β and ERK1-dependent phosphorylation of huntingtin during neuronal dysfunction and cell death in Huntington's disease.

ABSTRACT: Huntington's disease (HD) is a devastating neurodegenerative disorder that manifests from an N-terminal polyQ-expansion (>35) in the Huntingtin (HTT) gene leading to axonal degeneration and significant neuronal death. Despite evidence for a scaffolding role for HTT in membrane-related processes such as endocytosis, vesicle transport, and vesicle fusion, it remains unclear how polyQ-expansion alters membrane binding during these processes. Using quantitative Mass Spectrometry-based proteomics on HTT-containing light vesicle membranes isolated from healthy and HD iPSC-derived neurons, we found significant changes in the proteome and kinome of signal transduction, neuronal translation, trafficking, and axon guidance-related processes. Through a combination of in vitro kinase assays, Drosophil

SUBMITTER: Krzystek TJ 

PROVIDER: S-EPMC12015319 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature