Autophagy pathways in the treatment of prion diseases.
Curr Opin Pharmacol
; 44: 46-52, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-31096117
ABSTRACT
Prions use cellular machineries for autocatalytic propagation by conformational conversion of the cellular prion protein into the pathological isoform PrPSc. 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 PrPSc 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Doenças Priônicas
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article