Potential Therapeutic Value of the STING Inhibitors

Zhang, Shangran; Zheng, Runan; Sun, Hongbin

doi:10.3390/molecules28073127

Cited by 10 publications

(2 citation statements)

References 276 publications

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“…Notably, nitro fatty acids, which are protective in cardiovascular disease [ 70 , 71 ], also alkylate STING to prevent its activation [ 64 ]. Small molecule inhibitors of STING palmitoylation are being pursued for the treatment of autoinflammatory diseases including lupus erythematosus and psoriasis [ 62 , 63 , 68 ] and phase II clinical trials have been conducted for the treatment of focal segmental glomerulosclerosis with nitro fatty acids [ 62 ].…”

Section: Cardiomyocyte Signal Transductionmentioning

confidence: 99%

Regulation of cardiomyocyte intracellular trafficking and signal transduction by protein palmitoylation

Essandoh,

Teuber,

Brody

2024

Biochemical Society Transactions

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Despite the well-established functions of protein palmitoylation in fundamental cellular processes, the roles of this reversible post-translational lipid modification in cardiomyocyte biology remain poorly studied. Palmitoylation is catalyzed by a family of 23 zinc finger and Asp-His-His-Cys domain-containing S-acyltransferases (zDHHC enzymes) and removed by select thioesterases of the lysophospholipase and α/β-hydroxylase domain (ABHD)-containing families of serine hydrolases. Recently, studies utilizing genetic manipulation of zDHHC enzymes in cardiomyocytes have begun to unveil essential functions for these enzymes in regulating cardiac development, homeostasis, and pathogenesis. Palmitoylation co-ordinates cardiac electrophysiology through direct modulation of ion channels and transporters to impact their trafficking or gating properties as well as indirectly through modification of regulators of channels, transporters, and calcium handling machinery. Not surprisingly, palmitoylation has roles in orchestrating the intracellular trafficking of proteins in cardiomyocytes, but also dynamically fine-tunes cardiomyocyte exocytosis and natriuretic peptide secretion. Palmitoylation has emerged as a potent regulator of intracellular signaling in cardiomyocytes, with recent studies uncovering palmitoylation-dependent regulation of small GTPases through direct modification and sarcolemmal targeting of the small GTPases themselves or by modification of regulators of the GTPase cycle. In addition to dynamic control of G protein signaling, cytosolic DNA is sensed and transduced into an inflammatory transcriptional output through palmitoylation-dependent activation of the cGAS-STING pathway, which has been targeted pharmacologically in preclinical models of heart disease. Further research is needed to fully understand the complex regulatory mechanisms governed by protein palmitoylation in cardiomyocytes and potential emerging therapeutic targets.

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Section: Cardiomyocyte Signal Transductionmentioning

confidence: 99%

Regulation of cardiomyocyte intracellular trafficking and signal transduction by protein palmitoylation

Essandoh,

Teuber,

Brody

2024

Biochemical Society Transactions

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“…Дисплазия шейки матки -это предрак. Дисплазию рассматривают как патологический процесс, начинающийся в переходном метапластическом эпителии, который выражается в появлении атипичных клеток на фоне повышенной пролиферации базальных и парабазальных клеток [142]. Различают дисплазию легкой, средней и тяжелой степени.…”

Section: глава 1 современное состояние вопроса об особенностях иммунн...unclassified

Механизмы Межклеточных Взаимодействий В Слизистой Оболочке Репродуктивного Тракта Женщин В Возрастном Аспекте

Пуга,

Рева,

Коваль

et al. 2023

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Монография написана в соответствии с новейшими научными данными доступной литературы. Основная задача работы – в краткой форме представить необходимую информацию для успешной работы врачей клиницистов и специалистов в области клинической диагностики с целью создания фундаментальной платформы для изучения клинического материала, связанного с малигнизацией слизистой оболочки репродуктивного тракта женщин в постменопаузальном периоде. Представлены авторские материалы по иммунному гомеостазу слизистой оболочки репродуктивного тракта женщин, полученные в результате иммуногистохимических исследований. Использованная литература представлена современными изданиями по изучаемому предмету за последние 6 лет, включая монографии авторов. Для специалистов практического здравоохранения, а также студентов медицинских факультетов вузов и школ медицины университетов.

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Regulation of Type I Interferon and Autophagy in Immunity against Mycobacterium Tuberculosis: Role of CGAS and STING1

Malik,

Shariq,

Sheikh

et al. 2024

Advanced Biology

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Mycobacterium tuberculosis (M. tb) is a significant intracellular pathogen responsible for numerous infectious disease‐related deaths worldwide. It uses ESX‐1 T7SS to damage phagosomes and to enter the cytosol of host cells after phagocytosis. During infection, M. tb and host mitochondria release dsDNA, which activates the CGAS‐STING1 pathway. This pathway leads to the production of type I interferons and proinflammatory cytokines and activates autophagy, which targets and degrades bacteria within autophagosomes. However, the role of type I IFNs in immunity against M. tb is controversial. While previous research has suggested a protective role, recent findings from cgas‐sting1 knockout mouse studies have contradicted this. Additionally, a study using knockout mice and non‐human primate models uncovered a new mechanism by which neutrophils recruited to lung infections form neutrophil extracellular traps. Activating plasmacytoid dendritic cells causes them to produce type I IFNs, which interfere with the function of interstitial macrophages and increase the likelihood of tuberculosis. Notably, M. tb uses its virulence proteins to disrupt the CGAS‐STING1 signaling pathway leading to enhanced pathogenesis. Investigating the CGAS‐STING1 pathway can help develop new ways to fight tuberculosis.

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Potential Therapeutic Value of the STING Inhibitors

Cited by 10 publications

References 276 publications

Regulation of cardiomyocyte intracellular trafficking and signal transduction by protein palmitoylation

Regulation of cardiomyocyte intracellular trafficking and signal transduction by protein palmitoylation

Механизмы Межклеточных Взаимодействий В Слизистой Оболочке Репродуктивного Тракта Женщин В Возрастном Аспекте

Regulation of Type I Interferon and Autophagy in Immunity against Mycobacterium Tuberculosis: Role of CGAS and STING1

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