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Dual Role of Autophagy in Neurodegenerative Diseases: The Case of Amyotrophic Lateral Sclerosis

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Toxicity and Autophagy in Neurodegenerative Disorders

Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 9))

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult onset and fatal neurodegenerative disease. A major histophatological hallmark of the disease patient-derived tissue and ALS mouse models is the presence of protein aggregates containing misfolded specific proteins. Strategies to clear out these abnormal protein species are proposed as a possible target for disease intervention. Autophagy, a catabolic route that selective degradates abnormally-folded proteins by the lysosomal pathway, has emerged as an attractive target to treat neurodegenerative diseases, like ALS. Accumulating evidence indicates that autophagy impairment also occurs in ALS and can contribute to the neurodegenerative condition. In this article we discuss the evidence involving autophagy alteration associated to mutant ALS linked phenotype and the evidence that place autophagy as a therapeutic opportunity to treat this neurodegenerative disease.

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Acknowledgements

This work was funded by Millennium Institute No. P09-015-F, CONICYT grant USA2013-0003, ALS Therapy Alliance, and Muscular Dystrophy Association. We also thank FONDECYT 1140549, ECOS-CONICYT C13S02, The Michael J. Fox Foundation for Parkinson Research, Alzheimer’s Disease Association, and Foundation COPEC-UC (CH), Ring Initiative ACT1109, FONDEF grant No. D11I1007 (CH and SM), FONDECYT 11121524 (SM), CONICYT PAI 7912010006 (RLV) and CONICYT Master’s fellowship (LB).

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Authors and Affiliations

  1. Program of Cellular and Molecular Biology, Neurounion Biomedical Foundation, CENPAR, Independencia 1027, Santiago, Chile

    Leslie Bargsted, René L. Vidal, Claudio Hetz & Soledad Matus

  2. Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile

    Leslie Bargsted, René L. Vidal, Claudio Hetz & Soledad Matus

  3. Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, University of Chile, Santiago, Chile

    Leslie Bargsted & Claudio Hetz

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  1. Leslie Bargsted
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Correspondence to Claudio Hetz .

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  1. Bioquímica y Biología Molecular y Gen., Facultad de Enfermería y T.O., Cáceres, Spain

    José M. Fuentes

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Bargsted, L., Vidal, R., Hetz, C., Matus, S. (2015). Dual Role of Autophagy in Neurodegenerative Diseases: The Case of Amyotrophic Lateral Sclerosis. In: Fuentes, J. (eds) Toxicity and Autophagy in Neurodegenerative Disorders. Current Topics in Neurotoxicity, vol 9. Springer, Cham. https://doi.org/10.1007/978-3-319-13939-5_4

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