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Toward therapy of human prion diseases


Aguzzi, Adriano; Lakkaraju, Asvin K K; Frontzek, Karl (2018). Toward therapy of human prion diseases. Annual Review of Pharmacology and Toxicology, 58(1):331-351.

Abstract

Three decades after the discovery of prions as the cause of Creutzfeldt-Jakob disease and other transmissible spongiform encephalopathies, we are still nowhere close to finding an effective therapy. Numerous pharmacological interventions have attempted to target various stages of disease progression, yet none has significantly ameliorated the course of disease. We still lack a mechanistic understanding of how the prions damage the brain, and this situation results in a dearth of validated pharmacological targets. In this review, we discuss the attempts to interfere with the replication of prions and to enhance their clearance. We also trace some of the possibilities to identify novel targets that may arise with increasing insights into prion biology.

Abstract

Three decades after the discovery of prions as the cause of Creutzfeldt-Jakob disease and other transmissible spongiform encephalopathies, we are still nowhere close to finding an effective therapy. Numerous pharmacological interventions have attempted to target various stages of disease progression, yet none has significantly ameliorated the course of disease. We still lack a mechanistic understanding of how the prions damage the brain, and this situation results in a dearth of validated pharmacological targets. In this review, we discuss the attempts to interfere with the replication of prions and to enhance their clearance. We also trace some of the possibilities to identify novel targets that may arise with increasing insights into prion biology.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Toxicology
Life Sciences > Pharmacology
Language:English
Date:27 September 2018
Deposited On:28 Dec 2017 18:12
Last Modified:22 Nov 2023 08:21
Publisher:Annual Reviews
ISSN:0362-1642
Funders:ERC, SNF, CRPP University of Zurich, SystemsX.ch, Theodor und Ida Herzog-Egli Stiftung, Synapsis Foundation
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1146/annurev-pharmtox-010617-052745
PubMed ID:28961066
Project Information:
  • : FunderH2020
  • : Grant ID670958
  • : Project TitlePRION2020 - Function and malfunction of the prion protein
  • : Funder
  • : Grant ID
  • : Project TitleERC
  • : FunderSNSF
  • : Grant ID
  • : Project TitleSNF
  • : Funder
  • : Grant ID
  • : Project TitleCRPP University of Zurich
  • : Funder
  • : Grant ID
  • : Project TitleSystemsX.ch
  • : Funder
  • : Grant ID
  • : Project TitleTheodor und Ida Herzog-Egli Stiftung
  • : Funder
  • : Grant ID
  • : Project TitleSynapsis Foundation
  • Content: Accepted Version