Abnormal synaptic architecture in iPSC-derived neurons from a multi-generational family with genetic Creutzfeldt-Jakob disease.

ABSTRACT: Genetic prion diseases are caused by mutations in PRNP, which encodes the prion protein (PrP^C). Why these mutations are pathogenic, and how they alter the properties of PrP^C are poorly understood. We have consented and accessed 22 individuals of a multi-generational Israeli family harboring the highly penetrant E200K PRNP mutation and generated a library of induced pluripotent stem cells (iPSCs) representing nine carriers and four non-carriers. iPSC-derived neurons from E200K carriers display abnormal synaptic architecture characterized by misalignment of postsynaptic NMDA receptors with the cytoplasmic scaffolding protein PSD95. Differentiated neurons from mutation carriers do not produce PrP^Sc, the aggregated and infectious conformer of PrP, suggesting th

SUBMITTER: Gojanovich AD 

PROVIDER: S-EPMC11561462 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature