TDP-43 Puts the STING in ALS

John D Lee; Trent M Woodruff

doi:10.1016/j.tins.2020.12.001

TDP-43 Puts the STING in ALS

Trends Neurosci. 2021 Feb;44(2):81-82. doi: 10.1016/j.tins.2020.12.001. Epub 2020 Dec 20.

Authors

John D Lee¹, Trent M Woodruff²

Affiliations

¹ School of Biomedical Sciences, University of Queensland, St Lucia, Brisbane, QLD, 4072, Australia.
² School of Biomedical Sciences, University of Queensland, St Lucia, Brisbane, QLD, 4072, Australia; Queensland Brain Institute, University of Queensland, St Lucia, Brisbane, QLD, 4072, Australia. Electronic address: t.woodruff@uq.edu.au.

PMID: 33353765
DOI: 10.1016/j.tins.2020.12.001

Abstract

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.

Keywords: ALS; TDP-43; cGAS/STING; innate immunity; motor neuron disease; neurodegenerative disease; neuroinflammation.

Publication types

Research Support, Non-U.S. Gov't
Comment

MeSH terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Amyotrophic Lateral Sclerosis* / genetics
Bites and Stings*
DNA, Mitochondrial
DNA-Binding Proteins / genetics
Humans
Membrane Proteins / genetics
Nucleotidyltransferases / metabolism
Signal Transduction

Substances

DNA, Mitochondrial
DNA-Binding Proteins
Membrane Proteins
TARDBP protein, human
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Nucleotidyltransferases