An increasing amount of evidence shows that type I interferon response,which is induced by cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)and stimulator of interferon genes(STING)is closely assoc...An increasing amount of evidence shows that type I interferon response,which is induced by cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)and stimulator of interferon genes(STING)is closely associated with health and neuroinflammatory diseases.Abnormal activation or loss of control of the cGAS-STING axis affects the development of neuroinflammation.Thus,we examined its role in major neurological diseases,including traumatic brain injury,Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,multiple sclerosis,herpes simplex encephalitis,and ataxia-telangiectasia.Additionally,targeted intervention of the cGAS-STING axis to control neuroinflammation and treat related diseases has become the focus of current clinical research.This article describes the development of cGAS inhibitors and small molecules that target the cGAS-STING axis and explores the potential applications of STING inhibitors and agonists in clinical research.In summary,the cGAS-STING axis may impact neurological diseases more than a single protein or gene.Future studies should focus on elucidating the functional dynamics and regulatory networks of this axis and delineating its crosstalk with other signaling cascades.These investigations will provide mechanistic insights for developing targeted therapeutic strategies for associated disorders and potentially facilitate drug repurposing across diverse disease contexts.展开更多
基金supported by the National Natural Science Foundation of China,No.82301382the Natural Science Foundation of Hebei Province,No.H2022316001+1 种基金Government Funded Clinical Medicine Excellent Talents Project,No.ZF2023126the Postdoctoral Research Support Program for Clinical Medicine of Hebei Medical University,No.PD2023004(all to QZ).
文摘An increasing amount of evidence shows that type I interferon response,which is induced by cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)and stimulator of interferon genes(STING)is closely associated with health and neuroinflammatory diseases.Abnormal activation or loss of control of the cGAS-STING axis affects the development of neuroinflammation.Thus,we examined its role in major neurological diseases,including traumatic brain injury,Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,multiple sclerosis,herpes simplex encephalitis,and ataxia-telangiectasia.Additionally,targeted intervention of the cGAS-STING axis to control neuroinflammation and treat related diseases has become the focus of current clinical research.This article describes the development of cGAS inhibitors and small molecules that target the cGAS-STING axis and explores the potential applications of STING inhibitors and agonists in clinical research.In summary,the cGAS-STING axis may impact neurological diseases more than a single protein or gene.Future studies should focus on elucidating the functional dynamics and regulatory networks of this axis and delineating its crosstalk with other signaling cascades.These investigations will provide mechanistic insights for developing targeted therapeutic strategies for associated disorders and potentially facilitate drug repurposing across diverse disease contexts.
