Show simple item record

dc.contributor.authorMakarava, Natallia
dc.contributor.authorChang, Jennifer Chen-Yu
dc.contributor.authorMolesworth, Kara
dc.contributor.authorBaskakov, Ilia V
dc.date.accessioned2020-08-17T17:12:44Z
dc.date.available2020-08-17T17:12:44Z
dc.date.issued2020-08-03
dc.identifier.urihttp://hdl.handle.net/10713/13559
dc.description.abstractPosttranslational modifications are a common feature of proteins associated with neurodegenerative diseases including prion protein (PrPC), tau, and α-synuclein. Alternative self-propagating protein states or strains give rise to different disease phenotypes and display strain-specific subsets of posttranslational modifications. The relationships between strain-specific structure, posttranslational modifications, and disease phenotype are poorly understood. We previously reported that among hundreds of PrPC sialoglycoforms expressed by a cell, individual prion strains recruited PrPC molecules selectively, according to the sialylation status of their N-linked glycans. Here we report that transmission of a prion strain to a new host is accompanied by a dramatic shift in the selectivity of recruitment of PrPC sialoglycoforms, giving rise to a self-propagating scrapie isoform (PrPSc) with a unique sialoglycoform signature and disease phenotype. The newly emerged strain has the shortest incubation time to disease and is characterized by colocalization of PrPSc with microglia and a very profound proinflammatory response, features that are linked to a unique sialoglycoform composition of PrPSc. The current work provides experimental support for the hypothesis that strain-specific patterns of PrPSc sialoglycoforms formed as a result of selective recruitment dictate strain-specific disease phenotypes. This work suggests a causative relationship between a strain-specific structure, posttranslational modifications, and disease phenotype.en_US
dc.description.urihttps://doi.org/10.1172/JCI138677en_US
dc.language.isoen_USen_US
dc.publisherAmerican Society of Clinical Oncologyen_US
dc.relation.ispartofJournal of Clinical Investigationen_US
dc.subjectInfectious diseaseen_US
dc.subjectInnate immunityen_US
dc.subjectNeurodegenerationen_US
dc.subjectNeuroscienceen_US
dc.subjectPrionsen_US
dc.titlePosttranslational modifications define course of prion strain adaptation and disease phenotypeen_US
dc.typeArticleen_US
dc.identifier.doi10.1172/JCI138677
dc.identifier.pmid32484800
dc.source.volume130
dc.source.issue8
dc.source.beginpage4382
dc.source.endpage4395
dc.source.countryUnited States


This item appears in the following Collection(s)

Show simple item record