The cGAS-STING signaling pathway is modulated by urolithin A
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The cGAS-STING signaling pathway is modulated by urolithin A. / Madsen, H. B.; Park, J. H.; Chu, X.; Hou, Y.; Li, Z.; Rasmussen, L. J.; Croteau, D. L.; Bohr, V. A.; Akbari, M.
I: Mechanisms of Ageing and Development, Bind 217, 111897, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - The cGAS-STING signaling pathway is modulated by urolithin A
AU - Madsen, H. B.
AU - Park, J. H.
AU - Chu, X.
AU - Hou, Y.
AU - Li, Z.
AU - Rasmussen, L. J.
AU - Croteau, D. L.
AU - Bohr, V. A.
AU - Akbari, M.
N1 - Publisher Copyright: © 2023 The Authors
PY - 2024
Y1 - 2024
N2 - During aging, general cellular processes, including autophagic clearance and immunological responses become compromised; therefore, identifying compounds that target these cellular processes is an important approach to improve our health span. The innate immune cGAS-STING pathway has emerged as an important signaling system in the organismal defense against viral and bacterial infections, inflammatory responses to cellular damage, regulation of autophagy, and tumor immunosurveillance. These key functions of the cGAS-STING pathway make it an attractive target for pharmacological intervention in disease treatments and in controlling inflammation and immunity. Here, we show that urolithin A (UA), an ellagic acid metabolite, exerts a profound effect on the expression of STING and enhances cGAS-STING activation and cytosolic DNA clearance in human cell lines. Animal laboratory models and limited human trials have reported no obvious adverse effects of UA administration. Thus, the use of UA alone or in combination with other pharmacological compounds may present a potential therapeutic approach in the treatment of human diseases that involves aberrant activation of the cGAS-STING pathway or accumulation of cytosolic DNA and this warrants further investigation in relevant transgenic animal models.
AB - During aging, general cellular processes, including autophagic clearance and immunological responses become compromised; therefore, identifying compounds that target these cellular processes is an important approach to improve our health span. The innate immune cGAS-STING pathway has emerged as an important signaling system in the organismal defense against viral and bacterial infections, inflammatory responses to cellular damage, regulation of autophagy, and tumor immunosurveillance. These key functions of the cGAS-STING pathway make it an attractive target for pharmacological intervention in disease treatments and in controlling inflammation and immunity. Here, we show that urolithin A (UA), an ellagic acid metabolite, exerts a profound effect on the expression of STING and enhances cGAS-STING activation and cytosolic DNA clearance in human cell lines. Animal laboratory models and limited human trials have reported no obvious adverse effects of UA administration. Thus, the use of UA alone or in combination with other pharmacological compounds may present a potential therapeutic approach in the treatment of human diseases that involves aberrant activation of the cGAS-STING pathway or accumulation of cytosolic DNA and this warrants further investigation in relevant transgenic animal models.
KW - Autophagy
KW - CGAS-STING
KW - Endoplasmic reticulum
KW - Inflammation
KW - Urolithin A
U2 - 10.1016/j.mad.2023.111897
DO - 10.1016/j.mad.2023.111897
M3 - Journal article
C2 - 38109974
AN - SCOPUS:85180614292
VL - 217
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
SN - 0047-6374
M1 - 111897
ER -
ID: 377991930