Prion protein post-translational modifications modulate heparan sulfate binding and limit aggregate size in prion disease.

ABSTRACT: Many aggregation-prone proteins linked to neurodegenerative disease are post-translationally modified during their biogenesis. In vivo pathogenesis studies have suggested that the presence of post-translational modifications can shift the aggregate assembly pathway and profoundly alter the disease phenotype. In prion disease, the N-linked glycans and GPI-anchor on the prion protein (PrP) impair fibril assembly. However, the relevance of the two glycans to aggregate structure and disease progression remains unclear. Here we show that prion-infected knockin mice expressing an additional PrP glycan (tri-glycosylated PrP) develop new plaque-like deposits on neuronal cell membranes, along the subarachnoid space, and periventricularly, suggestive of high prion mobility and transit through the in

SUBMITTER: Callender JA 

PROVIDER: S-EPMC7425694 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature