The cGAS-STING pathway in aging and neurological diseases: From mechanisms to treatment

被引:0
作者
Li, Yi [1 ,2 ]
Chen, Yonghao [1 ,2 ]
Liu, Yunlong [1 ,2 ]
Wang, Chunmiao [1 ,2 ]
Fu, Xiuping [1 ,2 ]
Ren, Mengtian [1 ,2 ,3 ]
机构
[1] Tiangong Univ, Sch Chem, Tianjin 300387, Peoples R China
[2] Tiangong Univ, Sch Life Sci, Tianjin 300387, Peoples R China
[3] Tiangong Univ, Cangzhou Inst, Cangzhou 061000, Peoples R China
基金
中国国家自然科学基金;
关键词
cGAS-STING; Aging; Neurological diseases; Innate immunity; Therapeutic application; CYCLIC GMP-AMP; NF-KAPPA-B; MITOCHONDRIAL-DNA RELEASE; ACTIVATION; TREX1; PHOSPHORYLATION; 2ND-MESSENGER; INFLAMMATION; MICRONUCLEI; SYNTHASE;
D O I
10.1016/j.cellsig.2025.111978
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Among the numerous immune signal transduction pathways in the human body, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has attracted much attention due to its crucial role in sensing DNA within cells. In this article, we summarize the relationships between some phenomena of aging and the cGAS-STING pathway, including autophagy dysfunction and mitochondrial dysfunction, chronic inflammation and Chromosome instability and micronucleus DNA formation, and the roles of the cGAS-STING pathway in neurodegenerative diseases related to aging, neurological infections, and neuroimmune diseases. Finally, we analyze the potential therapeutic strategies of drugs that specifically inhibit the cGAS-STING pathway, such as cGAS inhibitors, Cyclic GMP-AMP (cGAMP) inhibitors, STING inhibitors and mitochondrial protectants. By introducing various diseases and their possible treatment options, this review deeply analyzes the impact of the cGAS-STING pathway on the aging process and neurological diseases, and explores its role in aging and neurological diseases as well as its potential therapeutic prospects.
引用
收藏
页数:12
相关论文
共 168 条
[1]   Cytosolic-DNA-Mediated, STING-Dependent Proinflammatory Gene Induction Necessitates Canonical NF-κB Activation through TBK1 [J].
Abe, Takayuki ;
Barber, Glen N. .
JOURNAL OF VIROLOGY, 2014, 88 (10) :5328-5341
[2]   cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING [J].
Ablasser, Andrea ;
Goldeck, Marion ;
Cavlar, Taner ;
Deimling, Tobias ;
Witte, Gregor ;
Roehl, Ingo ;
Hopfner, Karl-Peter ;
Ludwig, Janos ;
Hornung, Veit .
NATURE, 2013, 498 (7454) :380-+
[3]   Inhibition of the cGAS-STING pathway ameliorates the premature senescence hallmarks of Ataxia-Telangiectasia brain organoids [J].
Aguado, Julio ;
Chaggar, Harman K. ;
Gomez-Inclan, Cecilia ;
Shaker, Mohammed R. ;
Leeson, Hannah C. ;
Mackay-Sim, Alan ;
Wolvetang, Ernst J. .
AGING CELL, 2021, 20 (09)
[4]   The STING inhibitor (ISD-017) reduces glomerulonephritis in 129.B6.Fcgr2b-deficient mice [J].
Alee, Isara ;
Chantawichitwong, Papasara ;
Leelahavanichkul, Asada ;
Paludan, Soren R. ;
Pisitkun, Trairak ;
Pisitkun, Prapaporn .
SCIENTIFIC REPORTS, 2024, 14 (01)
[5]   Cutting Edge: Antimalarial Drugs Inhibit IFN-β Production through Blockade of Cyclic GMP-AMP Synthase-DNA Interaction [J].
An, Jie ;
Woodward, Joshua J. ;
Sasaki, Tomikazu ;
Minie, Mark ;
Elkon, Keith B. .
JOURNAL OF IMMUNOLOGY, 2015, 194 (09) :4089-4093
[6]   TDP-43 as a therapeutic target in neurodegenerative diseases: Focusing on motor neuron disease and frontotemporal dementia [J].
Babazadeh, Afshin ;
Rayner, Stephanie L. ;
Lee, Albert ;
Chung, Roger S. .
AGEING RESEARCH REVIEWS, 2023, 92
[7]  
Bao Y.B., 2025, Human Accumulation and Toxic Effects of Microplastics:A Critical Review
[8]   STING: infection, inflammation and cancer [J].
Barber, Glen N. .
NATURE REVIEWS IMMUNOLOGY, 2015, 15 (12) :760-770
[9]  
Baud D, 2017, LANCET, V390, P2099, DOI [10.1016/s0140-6736(17)31450-2, 10.1016/S0140-6736(17)31450-2]
[10]   Effect of VBIT-4 on the functional activity of isolated mitochondria and cell viability [J].
Belosludtsev, Konstantin N. ;
Ilzorkina, Anna I. ;
Matveeva, Lyudmila A. ;
V. Chulkov, Alexander ;
Semenova, Alena A. ;
V. Dubinin, Mikhail ;
V. Belosludtseva, Natalia .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2024, 1866 (05)