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

TDP-43 Puts the STING in ALS

John D Lee  1 , Trent M Woodruff  2
Affiliations
Comment

TDP-43 Puts the STING in ALS

John D Lee et al. Trends Neurosci. 2021 Feb.

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.

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Conflict of interest statement

Disclaimer Statement T.M.W. is developing complement inhibitors for neurological disease, and has consulted for companies developing innate immune system targeted therapies for ALS.

Comment on

  • TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS.
    Yu CH, Davidson S, Harapas CR, Hilton JB, Mlodzianoski MJ, Laohamonthonkul P, Louis C, Low RRJ, Moecking J, De Nardo D, Balka KR, Calleja DJ, Moghaddas F, Ni E, McLean CA, Samson AL, Tyebji S, Tonkin CJ, Bye CR, Turner BJ, Pepin G, Gantier MP, Rogers KL, McArthur K, Crouch PJ, Masters SL. Yu CH, et al. Cell. 2020 Oct 29;183(3):636-649.e18. doi: 10.1016/j.cell.2020.09.020. Epub 2020 Oct 7. Cell. 2020. PMID: 33031745 Free PMC article.

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