Hippo Signaling Pathway Dysregulation in Human Huntington's Disease Brain and Neuronal Stem Cells.

ABSTRACT: The Hippo signaling pathway is involved in organ size regulation and tumor suppression. Although inhibition of Hippo leads to tumorigenesis, activation of Hippo may play a role in neurodegeneration. Specifically, activation of the upstream regulator, mammalian sterile 20 (STE20)-like kinase 1 (MST1), reduces activity of the transcriptional co-activator Yes-Associated Protein (YAP), thereby mediating oxidative stress-induced neuronal death. Here, we investigated the possible role of this pathway in Huntington's disease (HD) pathogenesis. Our results demonstrate a significant increase in phosphorylated MST1, the active form, in post-mortem HD cortex and in the brains of CAG knock-in Hdh^Q111/Q111 mice. YAP nuclear localization was also decreased in HD post-mortem cortex and in neur

SUBMITTER: Mueller KA 

PROVIDER: S-EPMC6063913 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature