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Therapeutic targeting of autophagy in neurodegenerative and infectious diseases.


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Authors

Rubinsztein, David C 
Bento, Carla F 
Deretic, Vojo 

Abstract

Autophagy is a conserved process that uses double-membrane vesicles to deliver cytoplasmic contents to lysosomes for degradation. Although autophagy may impact many facets of human biology and disease, in this review we focus on the ability of autophagy to protect against certain neurodegenerative and infectious diseases. Autophagy enhances the clearance of toxic, cytoplasmic, aggregate-prone proteins and infectious agents. The beneficial roles of autophagy can now be extended to supporting cell survival and regulating inflammation. Autophagic control of inflammation is one area where autophagy may have similar benefits for both infectious and neurodegenerative diseases beyond direct removal of the pathogenic agents. Preclinical data supporting the potential therapeutic utility of autophagy modulation in such conditions is accumulating.

Description

Keywords

Autophagy, Communicable Diseases, Gene Expression Regulation, Humans, Models, Biological, Neurodegenerative Diseases, Oxazoles, Rilmenidine, Signal Transduction, Trehalose

Journal Title

J Exp Med

Conference Name

Journal ISSN

0022-1007
1540-9538

Volume Title

212

Publisher

Rockefeller University Press
Sponsorship
Wellcome Trust (095317/Z/11/Z)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (095317/Z/11/A)
We are grateful to the Wellcome Trust (095317/Z/11/Z Principal Research Fellowship to D.C. Rubinsztein and strategic award 100140), the National Institute for Health Research Biomedical Research Unit in Dementia at Addenbrooke’s Hospital (D.C. Rubinsztein), and the National Institutes of Health (AI042999 and AI111935; V. Deretic) for funding our work. D.C. Rubinsztein has received grant funding from MedImmune and is a scientific advisor for E3Bio and Bioblast.