The cGAS-STING signaling pathway is modulated by urolithin A
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https://hdl.handle.net/10037/35182Date
2023-12-16Type
Journal articleTidsskriftartikkel
Peer reviewed
Author
Madsen, Helena Borland; Park, J-H; Hou, Y; Li, Z; Rasmussen, Lene J.; Croteau, D. L.; Bohr, Vilhelm A.; Akbari, Mansour; Chu, X.Abstract
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.
Publisher
ElsevierCitation
Madsen, Park, Hou, Li, Rasmussen, Croteau, Bohr, Akbari. The cGAS-STING signaling pathway is modulated by urolithin A. Mechanisms of Ageing and Development. 2024;217Metadata
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