Role of cGAS-Sting Signaling in Alzheimer's Disease

被引：21

作者：

Govindarajulu, Manoj ^{[1
]}

Ramesh, Sindhu ^{[1
]}

Beasley, McNeil ^{[1
]}

Lynn, Graham ^{[1
]}

Wallace, Caleigh ^{[1
]}

Labeau, Sammie ^{[1
]}

Pathak, Suhrud ^{[1
]}

Nadar, Rishi ^{[1
]}

Moore, Timothy ^{[2
]}

Dhanasekaran, Muralikrishnan ^{[1
]}

机构：

[1] Auburn Univ, Harrison Coll Pharm, Dept Drug Discovery & Dev, Auburn, AL 36849 USA

[2] Auburn Univ, Harrison Coll Pharm, Res Programs, Units Adm,Drug Discovery & Dev, 2316 Walker Bldg, Auburn, AL 36849 USA

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 09期

关键词：

cGAS; STING; neuroinflammation; Alzheimer's disease; type-I IFN; MYELOID CELLS 2; CYTOSOLIC DNA; MITOCHONDRIAL-DNA; STRUCTURAL BASIS; I INTERFERON; IMMUNE; INFLAMMATION; DEGRADATION; SENESCENCE; RECEPTOR;

D O I：

10.3390/ijms24098151

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

There is mounting evidence that the development of Alzheimer's disease (AD) interacts extensively with immunological processes in the brain and extends beyond the neuronal compartment. Accumulation of misfolded proteins can activate an innate immune response that releases inflammatory mediators and increases the severity and course of the disease. It is widely known that type-I interferon-driven neuroinflammation in the central nervous system (CNS) accelerates the development of numerous acute and chronic CNS diseases. It is becoming better understood how the cyclic GMP-AMP synthase (cGAS) and its adaptor protein Stimulator of Interferon Genes (STING) triggers type-I IFN-mediated neuroinflammation. We discuss the principal elements of the cGAS-STING signaling pathway and the mechanisms underlying the association between cGAS-STING activity and various AD pathologies. The current understanding of beneficial and harmful cGAS-STING activity in AD and the current treatment pathways being explored will be discussed in this review. The cGAS-STING regulation offers a novel therapeutic opportunity to modulate inflammation in the CNS because it is an upstream regulator of type-I IFNs

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页数：16

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