Inhibitory targeting cGAS-STING-TBK1 axis: Emerging strategies for autoimmune diseases therapy

Min Zhang; Yan Zou; Xujun Zhou; Jinming Zhou

doi:10.3389/fimmu.2022.954129

Inhibitory targeting cGAS-STING-TBK1 axis: Emerging strategies for autoimmune diseases therapy

Front Immunol. 2022 Sep 12:13:954129. doi: 10.3389/fimmu.2022.954129. eCollection 2022.

Authors

Min Zhang^{1

2}, Yan Zou^{1

2}, Xujun Zhou^{1

2}, Jinming Zhou^{1

2}

Affiliations

¹ Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of Chemistry, Zhejiang Normal University, Jinhua, China.
² Drug development and innovation center, College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua, China.

Abstract

The cGAS-STING signaling plays an integral role in the host immune response, and the abnormal activation of cGAS-STING is highly related to various autoimmune diseases. Therefore, targeting the cGAS-STING-TBK1 axis has become a promising strategy in therapy of autoimmune diseases. Herein, we summarized the key pathways mediated by the cGAS-STING-TBK1 axis and various cGAS-STING-TBK1 related autoimmune diseases, as well as the recent development of cGAS, STING, or TBK1 selective inhibitors and their potential application in therapy of cGAS-STING-TBK1 related autoimmune diseases. Overall, the review highlights that inhibiting cGAS-STING-TBK1 signaling is an attractive strategy for autoimmune disease therapy.

Keywords: CGAS; STING; TBK1; autoimmune disease; inhibitor.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Autoimmune Diseases* / drug therapy
Humans
Membrane Proteins / metabolism
Nucleotidyltransferases / metabolism
Protein Serine-Threonine Kinases*
Signal Transduction / physiology

Substances

Membrane Proteins
Protein Serine-Threonine Kinases
TBK1 protein, human
Nucleotidyltransferases