Sialylation of Prion Protein Controls the Rate of Prion Amplification, the Cross-Species Barrier, the Ratio of PrP Glycoform and Prion Infectivity

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The central event underlying prion diseases involves conformational change of the cellular form of the prion protein (PrPC) into disease-associated, transmissible form (PrPSc). The amino acid sequence of PrPC and strain-specific structure of PrPSc are among the key parameters that control prion replication and transmission. The current study showed that PrPC posttranslational modification, specifically sialylation of N-linked glycans, plays a key role in regulating prion replication rate, infectivity, cross-species barrier and PrPSc glycoform ratio. A decrease in PrPC sialylation level increased the rate of prion replication in a strain-specific manner and reduced or eliminated a species barrier when prion replication was seeded by heterologous seeds. At the same time, a decrease in sialylation correlated with a drop in infectivity of PrPSc material produced in vitro. The current study also demonstrated that the PrPSc glycoform ratio, which is an important feature used for strain typing, is not only controlled by prion strain or host but also the sialylation status of PrPC. This study opens multiple new directions in prion research, including development of new therapeutic approaches.

Vyšlo v časopise: Sialylation of Prion Protein Controls the Rate of Prion Amplification, the Cross-Species Barrier, the Ratio of PrP Glycoform and Prion Infectivity. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004366
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004366

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