Open AccessCx43 hemichannels contribute to astrocyte-mediated toxicity in sporadic and familial ALS
Author(s) -
Akshata Almad,
Arens Taga,
Jessica Joseph,
Sarah K. Gross,
Connor Welsh,
Aneesh Patankar,
Jean Philippe Richard,
Khalil Rust,
Aayush Pokharel,
Caroline F. Plott,
Mauricio A. Lillo,
Raha Dastgheyb,
Kevin Eggan,
Norman J. Haughey,
Jorge E. Contreras,
Nicholas J. Maragakis
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2107391119
Subject(s) - astrocyte , connexin , gap junction , amyotrophic lateral sclerosis , neuroscience , neuroprotection , neurotoxicity , induced pluripotent stem cell , biology , microbiology and biotechnology , medicine , central nervous system , intracellular , pathology , disease , toxicity , biochemistry , embryonic stem cell , gene
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.