Autophagy pathways in the treatment of prion diseases

被引：20

作者：

Abdelaziz, Dalia H. ^{[1
,2
,3
]}

Abduirahman, Basant A. ^{[1
,2
,3
]}

Gilch, Sabine ^{[1
,2
,4
]}

Schatzl, Hermann M. ^{[1
,2
,3
]}

机构：

[1] Univ Calgary, Calgary Prion Res Unit, Calgary, AB, Canada

[2] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada

[3] Univ Calgary, Dept Comparat Biol Expt Med, Calgary, AB, Canada

[4] Univ Calgary, Dept Ecosyst & Publ Hlth, Calgary, AB, Canada

来源：

CURRENT OPINION IN PHARMACOLOGY | 2019年 / 44卷

基金：

美国国家卫生研究院;

关键词：

INDUCTION; PROTEIN; CELLS; RELEASE; CLEARANCE; INCREASES; BIOLOGY; PRPSC;

D O I：

10.1016/j.coph.2019.04.013

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：46 / 52

页数：7

共 48 条

[11] Targeting prion proteins in neurodegenerative disease [J].