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

Cytoplasmic accumulation of TDP-43 is a disease hallmark for many cases of amyotrophic lateral sclerosis (ALS), associated with a neuroinflammatory cytokine profile related to upregulation of nuclear factor κB (NF-κB) and type I interferon (IFN) pathways. Here we show that this inflammation is drive...

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Veröffentlicht in:	Cell 2020-10, Vol.183 (3), p.636-649.e18
Hauptverfasser:	Yu, Chien-Hsiung, Davidson, Sophia, Harapas, Cassandra R., Hilton, James B., Mlodzianoski, Michael J., Laohamonthonkul, Pawat, Louis, Cynthia, Low, Ronnie Ren Jie, Moecking, Jonas, De Nardo, Dominic, Balka, Katherine R., Calleja, Dale J., Moghaddas, Fiona, Ni, Erya, McLean, Catriona A., Samson, Andre L., Tyebji, Shiraz, Tonkin, Christopher J., Bye, Christopher R., Turner, Bradley J., Pepin, Genevieve, Gantier, Michael P., Rogers, Kelly L., McArthur, Kate, Crouch, Peter J., Masters, Seth L.
Format:	Artikel
Sprache:	eng
Schlagworte:	Alarmins - metabolism ALS Amyotrophic Lateral Sclerosis - metabolism Amyotrophic Lateral Sclerosis - pathology Animals Biochemistry & Molecular Biology Cell Biology cGAMP cGAS Cytoplasm - metabolism Disease Models, Animal Disease Progression DNA, Mitochondrial - metabolism DNA-Binding Proteins - metabolism HEK293 Cells Humans IFN Induced Pluripotent Stem Cells - metabolism Inflammation - metabolism Interferon Type I - metabolism Life Sciences & Biomedicine Membrane Proteins - metabolism Mice Mice, Inbred C57BL mitochondria Mitochondria - metabolism Mitochondrial Permeability Transition Pore - metabolism mPTP Nerve Degeneration - pathology neurodegeneration NF-kappa B - metabolism NF-κB Nucleotidyltransferases - metabolism Phosphotransferases (Alcohol Group Acceptor) Protein Subunits - metabolism Science & Technology Signal Transduction STING TDP-43
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