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Autophagy. 2018;14(4):733-737. doi: 10.1080/15548627.2018.1432327. Epub 2018 Mar 13.

Unraveling the role of motoneuron autophagy in ALS.

Valenzuela V1,2,3, Nassif M4, Hetz C1,2,3,5,6.

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a Biomedical Neuroscience Institute (BNI), Faculty of Medicine , University of Chile , Santiago , Chile.
b Center for Geroscience , Brain Health and Metabolism (GERO) , Santiago , Chile.
c Program of Cellular and Molecular Biology , Institute of Biomedical Sciences, University of Chile , Santiago , Chile.
d Center for Integrative Biology (CIB), Faculty of Sciences , Universidad Mayor , Santiago , Chile.
e Buck Institute for Research on Aging , Novato , CA , USA.
f Department of Immunology and Infectious Diseases , Harvard School of Public Health , Boston MA , USA.


In recent years, the role of autophagy in the pathogenesis of most neurodegenerative diseases has transitioned into a limbo of protective or detrimental effects. Genetic evidence indicates that mutations in autophagy-regulatory genes can result in the occurrence of amyotrophic lateral sclerosis (ALS), suggesting a physiological role of the pathway to motoneuron function. However, experimental manipulation of autophagy in ALS models led to conflicting results depending on the intervention strategy and the disease model used. A recent work by the Maniatis group systematically explored the role of cell-specific autophagy in motoneurons at different disease stages, revealing surprising and unexpected findings. Autophagy activity at early stages may contribute to maintaining the structure and function of neuromuscular junctions, whereas at later steps of the disease it has a pathogenic activity possibly involving cell-nonautonomous mechanisms related to glial activation. This new study adds a new layer of complexity in the field, suggesting an intricate interplay between proteostasis alterations, the time-differential function of autophagy in neurons, and muscle innervation in ALS.


ALS; SOD1; amyotrophic lateral sclerosis; autophagy; cell-nonautonomous; motoneuron; neuromuscular junction

[Available on 2019-03-13]

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