Abstract

Prion diseases are infectious and fatal neurodegenerative disorders of man and animals which are characterized by spongiform degeneration in the central nervous system. Prion propagation involves the endocytic pathway and endosomal and lysosomal compartments are implicated in trafficking and re-cycling as well as final degradation of prions. Shifting the equilibrium between propagation and lysosomal clearance to the latter impairs cellular prion load. This and earlier findings of autophagic vacuoles in correlation to prion infections both in in vitro and in vivo studies prompted us and others to analyze the role of autophagy in prion infection. Autophagy is a fundamental cellular bulk degradation process for e.g. organelles or cytoplasmic proteins which has many implications for physiology and patho-physiology of cells and whole organisms. In various neurodegenerative disease models mainly protective functions of autophagy were recently described. In this review, we focus on recent findings which correlate autophagy and its manipulations with prion infection scenarios, and discuss perspectives and future directions. The findings summarized here add to the knowledge of the role of autophagy in neurodegeneration and provide interesting new insight into how non-cytosolic aggregated proteins might be subjected to autophagic clearance.

Highlights

  • Prion diseases are infectious neurodegenerative disorders that can affect humans and animals

  • This results in a progressive spongiform degeneration of the central nervous system (CNS) which manifests itself in ataxia, behavioral changes and, in humans, a highly progressive loss of intellectual

  • In this review we focus on the cellular mechanism of autophagy, its regulation, some well-established methods to monitor autophagy, its implications in disease with emphasis on neurodegenerative disorders, and its putative role in prion infection scenarios

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Summary

Introduction

Prion diseases are infectious neurodegenerative disorders that can affect humans and animals. It was found that autophagic vacuoles are formed in neuronal perikarya, neurites and synapses in experimentally induced scrapie, Creutzfeldt-Jakob disease (CJD) and Gerstmann-SträusslerScheinker (GSS) syndrome (Liberski et al, 2004) and autophagic vacuoles were identified in synapses in various forms of human prion disease (Sikorska et al, 2004) Another interesting correlation between prion diseases and autophagy was observed in studies on scrg (scrapie responsive gene 1). In contrast to this assumption that autophagy plays a diseasepromoting role, it is quite conceivable that the observed increase in autophagic vacuoles in prion disease models is due to activation of the autophagic machinery as a defense

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Conclusions and future directions

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