Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 432, Issue 8, Pages 2799-2821Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2019.12.035
Keywords
lysosome; Alzheimer's disease; Parkinson's disease; polyglutamine diseases; amyotrophic lateral sclerosis
Categories
Funding
- UK Dementia Research Institute - MRC
- Alzheimer 's Research UK
- (Alzheimer 's Society), Roger de Spoelberch Foundation
- Cambridge Commonwealth, European & International Trust
- Romanian grant of Ministry of Research and Innovation CNCS eUEFISCDI [PNeIIIeP1-1.1-PD2016-1291]
- National Institutes of Health Oxford-Cambridge Scholars Program
- Cambridge Australia Scholarships
- Nehru Trust for Cambridge University
- Trinity-Henry Barlow Scholarship
- UK Medical Research Council
- Raymond and Beverly Sackler Fund
- MRC [UKDRI-2002] Funding Source: UKRI
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [ZIANS003038] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Autophagy is a major, conserved cellular pathway by which cells deliver cytoplasmic contents to lysosomes for degradation. Genetic studies have revealed extensive links between autophagy and neurodegenerative disease, and disruptions to autophagy may contribute to pathology in some cases. Autophagy degrades many of the toxic, aggregate-prone proteins responsible for such diseases, including mutant huntingtin (mHTT), alpha-synuclein (a-syn), tau, and others, raising the possibility that autophagy upregulation may help to reduce levels of toxic protein species, and thereby alleviate disease. This review examines autophagy induction as a potential therapy in several neurodegenerative diseases Alzheimer's disease, Parkinson's disease, polyglutamine diseases, and amyotrophic lateral sclerosis (ALS). Evidence in cells and in vivo demonstrates promising results in many disease models, in which autophagy upregulation is able to reduce the levels of toxic proteins, ameliorate signs of disease, and delay disease progression. However, the effective therapeutic use of autophagy induction requires detailed knowledge of how the disease affects the autophagy-lysosome pathway, as activating autophagy when the pathway cannot go to completion (e.g., when lysosomal degradation is impaired) may instead exacerbate disease in some cases. Investigating the interactions between autophagy and disease pathogenesis is thus a critical area for further research. (C) 2019 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available