Cx43 hemichannels contribute to astrocyte-mediated toxicity in sporadic and familial ALS-Reference-Cited by-同舟云学术

Cx43 hemichannels contribute to astrocyte-mediated toxicity in sporadic and familial ALS

Published:2022-03-21 Issue:13 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Almad Akshata A.¹^ORCID,Taga Arens¹^ORCID,Joseph Jessica¹,Gross Sarah K.¹^ORCID,Welsh Connor¹,Patankar Aneesh¹^ORCID,Richard Jean-Philippe¹^ORCID,Rust Khalil¹^ORCID,Pokharel Aayush¹^ORCID,Plott Caroline¹^ORCID,Lillo Mauricio²^ORCID,Dastgheyb Raha¹^ORCID,Eggan Kevin³,Haughey Norman¹^ORCID,Contreras Jorge E.²⁴^ORCID,Maragakis Nicholas J.¹^ORCID

Affiliation:

1. Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205

2. Department of Pharmacology, Physiology, & Neuroscience, New Jersey Medical School, Rutgers University, Newark, NJ 07101

3. Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138

4. Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA 95616

Abstract

Significance Our results demonstrate that connexin 43 hemichannels are the conduits for amyotrophic lateral sclerosis (ALS) astrocyte-mediated motor neuron toxicity and disease spread, acting as a common mechanism that can target both familial ALS and sporadic ALS populations. Furthermore, our present work provides proof of principle that tonabersat, as a drug already studied in clinical trials for other indications, could serve as a potential ALS therapeutic.

Funder

Amyotrophic Lateral Sclerosis Association

Maryland Stem Cell Research Fund

Packard Center for ALS Research at Johns Hopkins

U.S. Department of Defense

HHS | NIH | National Institute of Neurological Disorders and Stroke

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2107391119