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STING orchestrates the neuronal inflammatory stress response in multiple sclerosis

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STING orchestrates the neuronal inflammatory stress response in multiple sclerosis. / Woo, Marcel S; Mayer, Christina; Binkle-Ladisch, Lars; Sonner, Jana K; Rosenkranz, Sina C; Shaposhnykov, Artem; Rothammer, Nicola; Tsvilovskyy, Volodymyr; Lorenz, Svenja M; Raich, Lukas; Bal, Lukas C; Vieira, Vanessa; Wagner, Ingrid; Bauer, Simone; Glatzel, Markus; Conrad, Marcus; Merkler, Doron; Freichel, Marc; Friese, Manuel A.

In: CELL, Vol. 187, No. 15, 25.07.2024, p. 4043-4060.e30.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Woo, MS, Mayer, C, Binkle-Ladisch, L, Sonner, JK, Rosenkranz, SC, Shaposhnykov, A, Rothammer, N, Tsvilovskyy, V, Lorenz, SM, Raich, L, Bal, LC, Vieira, V, Wagner, I, Bauer, S, Glatzel, M, Conrad, M, Merkler, D, Freichel, M & Friese, MA 2024, 'STING orchestrates the neuronal inflammatory stress response in multiple sclerosis', CELL, vol. 187, no. 15, pp. 4043-4060.e30. https://doi.org/10.1016/j.cell.2024.05.031

APA

Woo, M. S., Mayer, C., Binkle-Ladisch, L., Sonner, J. K., Rosenkranz, S. C., Shaposhnykov, A., Rothammer, N., Tsvilovskyy, V., Lorenz, S. M., Raich, L., Bal, L. C., Vieira, V., Wagner, I., Bauer, S., Glatzel, M., Conrad, M., Merkler, D., Freichel, M., & Friese, M. A. (2024). STING orchestrates the neuronal inflammatory stress response in multiple sclerosis. CELL, 187(15), 4043-4060.e30. https://doi.org/10.1016/j.cell.2024.05.031

Vancouver

Woo MS, Mayer C, Binkle-Ladisch L, Sonner JK, Rosenkranz SC, Shaposhnykov A et al. STING orchestrates the neuronal inflammatory stress response in multiple sclerosis. CELL. 2024 Jul 25;187(15):4043-4060.e30. https://doi.org/10.1016/j.cell.2024.05.031

Bibtex

@article{c1fd3a67fb7c464389fec39c6e0bcae0,
title = "STING orchestrates the neuronal inflammatory stress response in multiple sclerosis",
abstract = "Inflammation-induced neurodegeneration is a defining feature of multiple sclerosis (MS), yet the underlying mechanisms remain unclear. By dissecting the neuronal inflammatory stress response, we discovered that neurons in MS and its mouse model induce the stimulator of interferon genes (STING). However, activation of neuronal STING requires its detachment from the stromal interaction molecule 1 (STIM1), a process triggered by glutamate excitotoxicity. This detachment initiates non-canonical STING signaling, which leads to autophagic degradation of glutathione peroxidase 4 (GPX4), essential for neuronal redox homeostasis and thereby inducing ferroptosis. Both genetic and pharmacological interventions that target STING in neurons protect against inflammation-induced neurodegeneration. Our findings position STING as a central regulator of the detrimental neuronal inflammatory stress response, integrating inflammation with glutamate signaling to cause neuronal cell death, and present it as a tractable target for treating neurodegeneration in MS.",
author = "Woo, {Marcel S} and Christina Mayer and Lars Binkle-Ladisch and Sonner, {Jana K} and Rosenkranz, {Sina C} and Artem Shaposhnykov and Nicola Rothammer and Volodymyr Tsvilovskyy and Lorenz, {Svenja M} and Lukas Raich and Bal, {Lukas C} and Vanessa Vieira and Ingrid Wagner and Simone Bauer and Markus Glatzel and Marcus Conrad and Doron Merkler and Marc Freichel and Friese, {Manuel A}",
note = "Copyright {\textcopyright} 2024 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2024",
month = jul,
day = "25",
doi = "10.1016/j.cell.2024.05.031",
language = "English",
volume = "187",
pages = "4043--4060.e30",
journal = "CELL",
issn = "0092-8674",
publisher = "Cell Press",
number = "15",

}

RIS

TY - JOUR

T1 - STING orchestrates the neuronal inflammatory stress response in multiple sclerosis

AU - Woo, Marcel S

AU - Mayer, Christina

AU - Binkle-Ladisch, Lars

AU - Sonner, Jana K

AU - Rosenkranz, Sina C

AU - Shaposhnykov, Artem

AU - Rothammer, Nicola

AU - Tsvilovskyy, Volodymyr

AU - Lorenz, Svenja M

AU - Raich, Lukas

AU - Bal, Lukas C

AU - Vieira, Vanessa

AU - Wagner, Ingrid

AU - Bauer, Simone

AU - Glatzel, Markus

AU - Conrad, Marcus

AU - Merkler, Doron

AU - Freichel, Marc

AU - Friese, Manuel A

N1 - Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2024/7/25

Y1 - 2024/7/25

N2 - Inflammation-induced neurodegeneration is a defining feature of multiple sclerosis (MS), yet the underlying mechanisms remain unclear. By dissecting the neuronal inflammatory stress response, we discovered that neurons in MS and its mouse model induce the stimulator of interferon genes (STING). However, activation of neuronal STING requires its detachment from the stromal interaction molecule 1 (STIM1), a process triggered by glutamate excitotoxicity. This detachment initiates non-canonical STING signaling, which leads to autophagic degradation of glutathione peroxidase 4 (GPX4), essential for neuronal redox homeostasis and thereby inducing ferroptosis. Both genetic and pharmacological interventions that target STING in neurons protect against inflammation-induced neurodegeneration. Our findings position STING as a central regulator of the detrimental neuronal inflammatory stress response, integrating inflammation with glutamate signaling to cause neuronal cell death, and present it as a tractable target for treating neurodegeneration in MS.

AB - Inflammation-induced neurodegeneration is a defining feature of multiple sclerosis (MS), yet the underlying mechanisms remain unclear. By dissecting the neuronal inflammatory stress response, we discovered that neurons in MS and its mouse model induce the stimulator of interferon genes (STING). However, activation of neuronal STING requires its detachment from the stromal interaction molecule 1 (STIM1), a process triggered by glutamate excitotoxicity. This detachment initiates non-canonical STING signaling, which leads to autophagic degradation of glutathione peroxidase 4 (GPX4), essential for neuronal redox homeostasis and thereby inducing ferroptosis. Both genetic and pharmacological interventions that target STING in neurons protect against inflammation-induced neurodegeneration. Our findings position STING as a central regulator of the detrimental neuronal inflammatory stress response, integrating inflammation with glutamate signaling to cause neuronal cell death, and present it as a tractable target for treating neurodegeneration in MS.

U2 - 10.1016/j.cell.2024.05.031

DO - 10.1016/j.cell.2024.05.031

M3 - SCORING: Journal article

C2 - 38878778

VL - 187

SP - 4043-4060.e30

JO - CELL

JF - CELL

SN - 0092-8674

IS - 15

ER -