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The role of the ESCRT pathway in prion disease
Author(s) -
Lawrence Jessica
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.542.14
Subject(s) - endosome , escrt , microvesicles , microbiology and biotechnology , neurodegeneration , biology , exosome , intracellular , autophagy , disease , microrna , gene , biochemistry , medicine , apoptosis , pathology
Prion diseases are infectious neurodegenerative disorders caused by PrP Sc , a misfolded and aggregated isoform of the cellular prion protein, PrP C . During late disease stages, PrP Sc spreads through the CNS, causing neurodegeneration, gliosis, and ultimately death, however the mechanisms of prion cell to cell transport remain poorly defined. Here we investigated the role of exosomes in the intercellular spread of prions. Exosomes are extracellular nanovesicles that originate from the endosomal pathway and are important for intercellular communication, transporting proteins and mRNA to nearby cells. Exosomes harbor infectious prions isolated immortalized cell lines and mice, and these exosomes efficiently cause prion disease in mice. Exosomes are produced by the ESCRT pathway, an endosomal pathway consisting of four protein complexes functioning sequentially. Previous research has shown that knocking down components of this pathway reduce prion conversion and release in vitro. We hypothesize that prions exploit the exosome pathway as the primary mechanism of prion spread within the CNS. We have manipulated the ESCRT pathway in neuronal cells to understand its role in both prion conversion and spread in vitro. We have discovered that inhibiting the initial stages of prion entry into endosomes severely impacts both prion generation as well as autophagic degradation pathways. Support or Funding Information NIH F31 NS103588 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .