TDP-43 Puts the STING in ALS

In a recent study, Yu et al. demonstrated that TAR DNA-binding protein of 43 kDa (TDP-43) causes inflammation in amyotrophic lateral sclerosis (ALS) by triggering mitochondrial (mt)DNA release into the cytoplasm, which subsequently activates the cytoplasmic DNA-sensing cyclic GMP-AMP synthase (cGAS)...

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Bibliographic Details
Published inTrends in neurosciences (Regular ed.) Vol. 44; no. 2; pp. 81 - 82
Main Authors Lee, John D., Woodruff, Trent M.
Format Journal Article
LanguageEnglish
Published England Elsevier Ltd 01.02.2021
Subjects
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
ALS
Amyotrophic Lateral Sclerosis - genetics
Bites and Stings
cGAS/STING
DNA, Mitochondrial
DNA-Binding Proteins - genetics
Humans
innate immunity
Membrane Proteins - genetics
motor neuron disease
neurodegenerative disease
neuroinflammation
Nucleotidyltransferases - metabolism
Signal Transduction
TDP-43
motor neuron disease
neurodegenerative disease
innate immunity
neuroinflammation
TDP-43
cGAS/STING
ALS
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Summary:In a recent study, Yu et al. demonstrated that TAR DNA-binding protein of 43 kDa (TDP-43) causes inflammation in amyotrophic lateral sclerosis (ALS) by triggering mitochondrial (mt)DNA release into the cytoplasm, which subsequently activates the cytoplasmic DNA-sensing cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway. These results suggest that inhibition of cGAS/STING could help mitigate inflammation-related neuropathology in ALS.
ISSN:0166-2236
1878-108X
DOI:10.1016/j.tins.2020.12.001