SLIRP promotes autoimmune diseases by amplifying antiviral signaling via positive feedback regulation DOI Creative Commons
Doyeong Ku,

Yewon Yang,

Young-Ran Park

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 2, 2024

SUMMARY The abnormal innate immune response is a prominent feature underlying autoimmune diseases. One emerging factor that can trigger dysregulated activation cytosolic mitochondrial double-stranded RNAs (mt-dsRNAs). However, the mechanism by which mt-dsRNAs stimulate responses remains poorly understood. Here, we discover SRA stem-loop interacting RNA binding protein (SLIRP) as key amplifier of mt-dsRNA-triggered antiviral signals. In diseases, SLIRP commonly upregulated, and targeted knockdown dampens interferon response. We find melanoma differentiation-associated gene 5 (MDA5) exogenous dsRNAs upregulates SLIRP, then stabilizes promotes their release to activate MDA5 further, augmenting Furthermore, downregulation partially rescues interferon-stimulated expression in patients’ primary cells makes vulnerable certain viral infections. Our study unveils pivotal mediator through positive feedback amplification signaling.

Язык: Английский

The Pharmacological Properties of Red Grape Polyphenol Resveratrol: Clinical Trials and Obstacles in Drug Development DOI Open Access
Mohd Farhan, Asim Rizvi

Nutrients, Год журнала: 2023, Номер 15(20), С. 4486 - 4486

Опубликована: Окт. 23, 2023

Resveratrol is a stilbenoid from red grapes that possesses strong antioxidant activity. has been shown to have anticancer activity, making it promising drug for the treatment and prevention of numerous cancers. Several in vitro vivo investigations validated resveratrol’s capabilities, demonstrating its ability block all steps carcinogenesis (such as initiation, promotion, progression). Additionally, resveratrol found auxiliary pharmacological effects such anti-inflammatory, cardioprotective, neuroprotective Despite properties, several obstacles, poor solubility bioavailability, well adverse effects, continue be key obstacles development. This review critically evaluates clinical trials date aims develop framework into clinically viable drug.

Язык: Английский

Процитировано

34

The Interplay of Mitochondrial Dysfunction in Oral Diseases: Recent Updates in Pathogenesis and Therapeutic Implications DOI

Al-Hassan Soliman Wadan,

Mohamed Abdelsattar Ahmed,

Abdelnaser Hussein Ahmed

и другие.

Mitochondrion, Год журнала: 2024, Номер 78, С. 101942 - 101942

Опубликована: Авг. 6, 2024

Язык: Английский

Процитировано

8

Mitochondrial nucleic acids in innate immunity and beyond DOI Creative Commons
Jimin Yoon, Sujin Kim, Mihye Lee

и другие.

Experimental & Molecular Medicine, Год журнала: 2023, Номер 55(12), С. 2508 - 2518

Опубликована: Дек. 1, 2023

Abstract Mitochondria participate in a wide range of cellular processes. One essential function mitochondria is to be platform for antiviral signaling proteins during the innate immune response viral infection. Recently, studies have revealed that mitochondrion-derived DNAs and RNAs are recognized as non-self molecules act immunogenic ligands. More importantly, cytosolic release these mitochondrial nucleic acids (mt-NAs) closely associated with pathogenesis human diseases accompanying aberrant activation. The (mtDNAs) via BAX/BAK activation and/or VDAC1 oligomerization activates inflammasome assembly. In addition, double-stranded (mt-dsRNAs) sensed by pattern recognition receptors cytosol induce type I interferon expression initiate apoptotic programs. Notably, mt-NAs also mediate adipocyte differentiation contribute mitogenesis thermogenesis. this review, we summarize recent pathways regulated mt-NAs, emerging physiological roles mt-NAs.

Язык: Английский

Процитировано

14

Mitochondrial Dysfunction in the Pathogenesis and Treatment of Oral Inflammatory Diseases DOI Open Access
Zhili Dong, Liping Wu, Hong Hong

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(20), С. 15483 - 15483

Опубликована: Окт. 23, 2023

Oral inflammatory diseases (OIDs) include many common such as periodontitis and pulpitis. The causes of OIDs consist microorganism, trauma, occlusal factors, autoimmune dis-eases radiation therapy. When treated unproperly, not only affect oral health but also pose threat to people’s overall condition. Therefore, identifying at an early stage exploring new therapeutic strategies are important tasks for oral-related research. Mitochondria crucial organelles cellular activities disruptions mitochondrial function metabolism indirectly influence life span. Mitochondrial dysfunction has been implicated in polygenic diseases, including cardiovascular neurodegenerative diseases. Recently, increasing evidence suggests that plays a critical role the development progression its associated systemic In this review, we elucidated insights into involvement responses OIDs. We summarized recent research progresses on treatment targeting discussed underlying mechanisms.

Язык: Английский

Процитировано

12

Taurine can restrict mtdsRNA mediated pyroptosis by enhancing mitophagy in nucleus pulposus cells DOI
Zixuan Ou, Junyu Wei,

Bide Tong

и другие.

Опубликована: Апрель 15, 2025

Abstract Mitochondrial double-stranded RNA (mtdsRNA), a long-stranded molecule generated by bidirectional transcription of the circular mitochondrial genome, can trigger type 1 interferon response activating pattern recognition receptors in cytoplasm during dysfunction. However, its regulatory and pathogenic mechanisms intervertebral disc degeneration are poorly understood. Here, we showed that mtdsRNA was abnormally elevated degenerative nucleus pulposus tissues. Furthermore, found leakage into could cause MAVS oligomerization binding to RLRs, oligomerized then promote cell pyroptosis NLRP3. To further elucidate upstream mechanism mtdsRNA, performed untargeted metabolomics analysis, which revealed downregulation taurine under external stimuli drive an imbalance homeostasis. RNA-seq exogenous supplementation with protected cells from mtdsRNA-induced increasing mitophagy. In conclusion, our study links metabolism, nucleic acids suggests is important causative potential therapeutic target degeneration.

Язык: Английский

Процитировано

0

SLIRP promotes autoimmune diseases by amplifying antiviral signaling via positive feedback regulation DOI Creative Commons
Doyeong Ku,

Yewon Yang,

Young-Ran Park

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 2, 2024

SUMMARY The abnormal innate immune response is a prominent feature underlying autoimmune diseases. One emerging factor that can trigger dysregulated activation cytosolic mitochondrial double-stranded RNAs (mt-dsRNAs). However, the mechanism by which mt-dsRNAs stimulate responses remains poorly understood. Here, we discover SRA stem-loop interacting RNA binding protein (SLIRP) as key amplifier of mt-dsRNA-triggered antiviral signals. In diseases, SLIRP commonly upregulated, and targeted knockdown dampens interferon response. We find melanoma differentiation-associated gene 5 (MDA5) exogenous dsRNAs upregulates SLIRP, then stabilizes promotes their release to activate MDA5 further, augmenting Furthermore, downregulation partially rescues interferon-stimulated expression in patients’ primary cells makes vulnerable certain viral infections. Our study unveils pivotal mediator through positive feedback amplification signaling.

Язык: Английский

Процитировано

1