Autophagy pathways in the treatment of prion diseases. (February 2019)

• Record Type: Journal Article
• Authors: Abdelaziz, Dalia H; Abdulrahman, Basant A; Gilch, Sabine; Schatzl, Hermann M
• Is Part Of: Current opinion in pharmacology. Volume 44(2019)
• Page Start: 46
• Page End: 52
• Publication Date: 2019-02
• Subjects: Pharmacology -- Periodicals; Pharmaceutical Preparations -- Periodicals; Drug Therapy -- Periodicals; Biopharmaceutics -- Periodicals; Pharmacologie -- Périodiques; Pharmacology; Periodicals; 615.105
• DOI: 10.1016/j.coph.2019.04.013
• Languages: English
• ISSNs: 1471-4892

Abstract

Highlights: Prions are misfolded proteins causing fatal neurodegenerative diseases. Autophagy dictates the fate of PrP Sc in various contexts in prion infection. Autophagy facilitates delivery of prions to lysosomal degradation. Increase in autophagy reduces the exosomal release of prion infectivity. Pharmacological stimulation of autophagy is beneficial in prion infection. Abstract : Prions use cellular machineries for autocatalytic propagation by conformational conversion of the cellular prion protein into the pathological isoform PrP Sc . Autophagy is a basic cellular degradation and recycling machinery that delivers cargo to lysosomes. Increase of autophagic flux in cells results in enhanced delivery of PrP Sc in late endosomes to lysosomal degradation, providing a therapeutic target for prion diseases. Application of chemical enhancers of autophagy to cell or mouse models of prion infection provided a solid experimental proof-of-concept for this anti-prion strategy. In addition, increasing autophagy also reduces exosomal release of prions and transfer of prion infectivity between cells. Taken together, pharmacological induction of autophagy is a promising target for containing prion diseases, and ideal candidate for future combination therapies.