Toward Therapy of Human Prion Diseases

2017/09/29 by Adriano Aguzzi, Asvin KK Lakkaraju, Karl Frontzek · 1 citation
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Prion Diseases and Protein Misfolding #Neurological diseases and metabolism #Nuclear Receptors and Signaling

paper · doi:10.1146/annurev-pharmtox-010617-052745

openalex publication_date 2017/09/29 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28

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.

Citations

• Safety and efficacy of quinacrine in human prion disease (PRION-1 study): a patient-preference trial
• Oral Treatment Targeting the Unfolded Protein Response Prevents Neurodegeneration and Clinical Disease in Prion-Infected Mice
• Novel Proteinaceous Infectious Particles Cause Scrapie
• Trehalose, a Novel mTOR-independent Autophagy Enhancer, Accelerates the Clearance of Mutant Huntingtin and α-Synuclein
• Mechanisms of cross‐talk between the ubiquitin‐proteasome and autophagy‐lysosome systems
• Unique drug screening approach for prion diseases identifies tacrolimus and astemizole as antiprion agents

Cited by

• Prion [wikipedia]