Journal article
TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS
CH Yu, S Davidson, CR Harapas, JB Hilton, MJ Mlodzianoski, P Laohamonthonkul, C Louis, RRJ Low, J Moecking, D De Nardo, KR Balka, DJ Calleja, F Moghaddas, E Ni, CA McLean, AL Samson, S Tyebji, CJ Tonkin, CR Bye, BJ Turner Show all
Cell | CELL PRESS | Published : 2020
Open access
Abstract
TDP-43 causes inflammation in ALS by stimulating mitochondrial DNA release, which is subsequently sensed by the cytosolic cGAS/STING pathway, suggesting that inhibition of cGAS/STING could help alleviate inflammation-related damage in ALS.
Grants
Awarded by Victorian Brain Bank
Funding Acknowledgements
We thank R. Crawley and S. Russo for outstanding animal husbandry. We thank J. Brouwer, G. Dewson, P. Czabotar (WEHI), T. Sadler (Hudson Institute), and B. Kile (Monash University) for intellectual contributions and experimental assistance. Human tissue samples were obtained from the Victorian Brain Bank with assistance from Fairlie Hinton and Geoff Pavey. This work was supported by Australian National Health and Medical Research Council (NHMRC) project grants 1057815 and 1099262, fellowships to S.L.M. and P.J.C., an Independent Research Institutes Infrastructure Support Scheme grant (361646), a research gift (Brain Foundation), and a FightMND Drug Screening Program grant (to B.J.T.). This work was also supported by fellowships from the Victorian Endowment for Science Knowledge and Innovation (to S.L.M.), an HHMIWellcome International Research Scholarship (to S.L.M.), the Sylvia and Charles Viertel Foundation (to S.L.M.), the Australian Research Council (140100594 Future Fellowship to M.P.G.), a National Health and Medical Research Council Early Career Fellowship (SD GNT1143412), fellowship Fonds de Recherche du Quebec -Sante (GP FRSQ 35071), a WEHI Centenary Fellowship (to C.-H.Y.), an Ormond College Thwaites Gutch Fellowship in Physiology (to C.-H.Y.), the Motor Neurone Disease Research Institute of Australia (Betty Laidlaw and Superball XI MND research grants), the Australian Phenomics Network, the Ian Potter Centre for Genomics and Personalized Medicine, and a Victorian State Government operational infrastructure support grant. S.L.M. receives funding from GlaxoSmithKline.