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TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS

Authors
  • Yu, Chien-Hsiung1, 2
  • Davidson, Sophia1, 2
  • Harapas, Cassandra R.1, 2
  • Hilton, James B.3, 4
  • Mlodzianoski, Michael J.5, 2
  • Laohamonthonkul, Pawat1, 2
  • Louis, Cynthia1, 2
  • Low, Ronnie Ren Jie6, 2
  • Moecking, Jonas1, 2, 7
  • De Nardo, Dominic1, 2, 8
  • Balka, Katherine R.1, 2, 8
  • Calleja, Dale J.1, 2
  • Moghaddas, Fiona1, 2, 9
  • Ni, Erya10, 2
  • McLean, Catriona A.11
  • Samson, Andre L.1, 2
  • Tyebji, Shiraz10, 2
  • Tonkin, Christopher J.10, 2
  • Bye, Christopher R.4
  • Turner, Bradley J.4
  • And 6 more
  • 1 Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
  • 2 Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia
  • 3 Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, VIC 3010, Australia
  • 4 Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia
  • 5 Centre for Dynamic Imaging, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
  • 6 Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
  • 7 Institute of Structural Biology, University of Bonn, 53127 Bonn, Germany
  • 8 Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3168, Australia
  • 9 Department of Immunology and Allergy, The Royal Melbourne Hospital, Parkville, VIC 3052, Australia
  • 10 Infection and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
  • 11 Anatomical Pathology, The Alfred Hospital, Melbourne, VIC 3004, Australia
  • 12 Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia
  • 13 Australia
  • 14 Immunology Laboratory, Guangzhou Institute of Paediatrics, Guangzhou Women and Children’s Medical Centre, Guangzhou, Guangdong 510623, China
Type
Published Article
Journal
Cell
Publisher
Cell Press
Publication Date
Oct 29, 2020
Volume
183
Issue
3
Pages
636–649
Identifiers
DOI: 10.1016/j.cell.2020.09.020
PMID: 33031745
PMCID: PMC7599077
Source
PubMed Central
Keywords
Disciplines
  • Article
License
Unknown

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.

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