4-Phenylbutyrate ameliorates apoptotic neural cell death in Down syndrome by reducing protein aggregates.

ABSTRACT: Individuals with Down syndrome (DS) commonly show unique pathological phenotypes throughout their life span. Besides the specific effects of dosage-sensitive genes on chromosome 21, recent studies have demonstrated that the gain of a chromosome exerts an adverse impact on cell physiology, regardless of the karyotype. Although dysregulated transcription and perturbed protein homeostasis are observed in common in human fibroblasts with trisomy 21, 18, and 13, whether and how this aneuploidy-associated stress acts on other cell lineages and affects the pathophysiology are unknown. Here, we investigated cellular stress responses in human trisomy 21 and 13 neurons differentiated from patient-derived induced pluripotent stem cells. Neurons of both trisomies showed increased vulnerability to apop

SUBMITTER: Hirata K 

PROVIDER: S-EPMC7441064 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature