Overexpression of quality control proteins reduces prion conversion in prion-infected cells

The Journal of Biological Chemistry
Simrika ThapaHermann M Schätzl

Abstract

Prion diseases are fatal infectious neurodegenerative disorders in humans and other animals and are caused by misfolding of the cellular prion protein (PrPC) into the pathological isoform PrPSc These diseases have the potential to transmit within or between species, including zoonotic transmission to humans. Elucidating the molecular and cellular mechanisms underlying prion propagation and transmission is therefore critical for developing molecular strategies for disease intervention. We have shown previously that impaired quality control mechanisms directly influence prion propagation. In this study, we manipulated cellular quality control pathways in vitro by stably and transiently overexpressing selected quality control folding (ERp57) and cargo (VIP36) proteins and investigated the effects of this overexpression on prion propagation. We found that ERp57 or VIP36 overexpression in persistently prion-infected neuroblastoma cells significantly reduces the amount of PrPSc in immunoblots and prion-seeding activity in the real-time quaking-induced conversion (RT-QuIC) assay. Using different cell lines infected with various prion strains confirmed that this effect is not cell type- or prion strain-specific. Moreover, de novo prion...Continue Reading

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Citations

Jan 26, 2020·Molecular Neurobiology·Simrika ThapaHermann M Schatzl
Aug 3, 2019·Scientific Reports·Rupali WaliaHermann M Schatzl
Feb 6, 2021·Acta Neuropathologica Communications·Pablo RozasDanilo B Medinas
Jan 13, 2022·Neural Regeneration Research·Waqas TahirHermann M Schatzl

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Methods Mentioned

BETA
fluorescence microscopy
transfection
PCR
detergent
solubility assay
confocal microscopy
protein assay

Software Mentioned

GraphPad
ImageJ
Unicorn
GraphPad Prism
RT

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