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Cellular models for discovering prion disease therapeutics: Progress and challenges
Author(s) -
Krance Saffire H.,
Luke Russell,
Shenouda Marc,
Israwi Ahmad R.,
Colpitts Sarah J.,
Darwish Lina,
Strauss Maximilian,
Watts Joel C.
Publication year - 2020
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14956
Subject(s) - disease , prion protein , biology , virology , infectious disease (medical specialty) , neuroscience , neurodegeneration , computational biology , medicine , pathology
Prions, which cause fatal neurodegenerative disorders such as Creutzfeldt‐Jakob disease, are misfolded and infectious protein aggregates. Currently, there are no treatments available to halt or even delay the progression of prion disease in the brain. The infectious nature of prions has resulted in animal paradigms that accurately recapitulate all aspects of prion disease, and these have proven to be instrumental for testing the efficacy of candidate therapeutics. Nonetheless, infection of cultured cells with prions provides a much more powerful system for identifying molecules capable of interfering with prion propagation. Certain lines of cultured cells can be chronically infected with various types of mouse prions, and these models have been used to unearth candidate anti‐prion drugs that are at least partially efficacious when administered to prion‐infected rodents. However, these studies have also revealed that not all types of prions are equal, and that drugs active against mouse prions are not necessarily effective against prions from other species. Despite some recent progress, the number of cellular models available for studying non‐mouse prions remains limited. In particular, human prions have proven to be particularly challenging to propagate in cultured cells, which has severely hindered the discovery of drugs for Creutzfeldt‐Jakob disease. In this review, we summarize the cellular models that are presently available for discovering and testing drugs capable of blocking the propagation of prions and highlight challenges that remain on the path towards developing therapies for prion disease.

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