Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model

Kevin A Guttenplan; Maya K Weigel; Drew I Adler; Julien Couthouis; Shane A Liddelow; Aaron D Gitler; Ben A Barres

doi:10.1038/s41467-020-17514-9

Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model

Nat Commun. 2020 Jul 27;11(1):3753. doi: 10.1038/s41467-020-17514-9.

Authors

Kevin A Guttenplan^{1

2}, Maya K Weigel³, Drew I Adler⁴, Julien Couthouis⁵, Shane A Liddelow^#^{4

6

7}, Aaron D Gitler^#⁸, Ben A Barres^#³

Affiliations

¹ Department of Neurobiology, School of Medicine, Stanford University, Stanford, 94305, CA, USA. kguttenp@stanford.edu.
² Department of Genetics, School of Medicine, Stanford University, Stanford, 94305, CA, USA. kguttenp@stanford.edu.
³ Department of Neurobiology, School of Medicine, Stanford University, Stanford, 94305, CA, USA.
⁴ Neuroscience Institute, NYU School of Medicine, New York, NY, 10016, USA.
⁵ Department of Genetics, School of Medicine, Stanford University, Stanford, 94305, CA, USA.
⁶ Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY, 10016, USA.
⁷ Department of Ophthalmology, NYU School of Medicine, New York, NY, 10016, USA.
⁸ Department of Genetics, School of Medicine, Stanford University, Stanford, 94305, CA, USA. agitler@stanford.edu.

^# Contributed equally.

Abstract

Reactive astrocytes have been implicated in the pathogenesis of neurodegenerative diseases, including a non-cell autonomous effect on motor neuron survival in ALS. We previously defined a mechanism by which microglia release three factors, IL-1α, TNFα, and C1q, to induce neurotoxic astrocytes. Here we report that knocking out these three factors markedly extends survival in the SOD1^G93A ALS mouse model, providing evidence for gliosis as a potential ALS therapeutic target.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amyotrophic Lateral Sclerosis / metabolism*
Amyotrophic Lateral Sclerosis / pathology*
Animals
Astrocytes / metabolism*
Complement C1q / metabolism*
Complement C3 / metabolism
Disease Models, Animal
Disease Progression*
Humans
Interleukin-1alpha / metabolism*
Mice, Inbred C57BL
Mice, Knockout
Microglia
Superoxide Dismutase-1 / metabolism
Tumor Necrosis Factor-alpha / metabolism*

Substances

Complement C3
Interleukin-1alpha
Tumor Necrosis Factor-alpha
Complement C1q
Superoxide Dismutase-1

Abstract

Publication types

MeSH terms

Substances

Grants and funding