FNDC5/Irisin protects neurons through Caspase3 and Bax pathways

Zhang, Qiu‐Xia; Zhang, Lin‐Jie; Zhao, Ning; Chang, Sheng‐Hui; Yang, Li

doi:10.1002/cbf.3912

Cited by 3 publications

(6 citation statements)

References 47 publications

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“…The positive effect of irisin on cell viability under AP induction was thwarted by the specific PPARγ antagonist G3335 ( Figure 5 F), further indicating that the activation of PPARγ, possibly via the PPARγ-PGC1α-FNDC5 pathway, is related to the improvement in cell viability under exogenous irisin supplementation. A few studies reported irisin beneficial effect on apoptotic status in several cells, including endocrine pancreas cells [ 53 , 85 , 86 ]. The positive effect of irisin on the cellular viability observed in our study ( Figure 5 F–G) might be downstream of the PPARγ-PGC1α-FNDC5 pathway, due to the modulation of pro- and anti-apoptotic markers activated under stress conditions in favor of pro-survival agents.…”

Section: Discussionmentioning

confidence: 99%

Irisin Ameliorate Acute Pancreatitis and Acinar Cell Viability through Modulation of the Unfolded Protein Response (UPR) and PPARγ-PGC1α-FNDC5 Pathways

Horwitz,

Birk

2024

Biomolecules

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Acute pancreatitis (AP) entails pancreatic inflammation, tissue damage and dysregulated enzyme secretion, including pancreatic lipase (PL). The role of irisin, an anti-inflammatory and anti-apoptotic cytokine, in AP and exocrine pancreatic stress is unclear. We have previously shown that irisin regulates PL through the PPARγ-PGC1α-FNDC5 pathway. In this study, we investigated irisin and irisin’s pathway on AP in in vitro (AR42J-B13) and ex vivo (rat primary acinar) models using molecular, biochemical and immunohistochemistry methodology. Pancreatitis induction (cerulein (cer)) resulted in a significant up-regulation of the PPARγ-PGC1α-FNDC5 axis, PL expression and secretion and endoplasmic reticulum (ER) stress unfolded protein response (UPR) signal-transduction markers (CHOP, XBP-1 and ATF6). Irisin addition in the cer-pancreatitis state resulted in a significant down-regulation of the PPARγ-PGC1α-FNDC5 axis, PPARγ nucleus-translocation and inflammatory state (TNFα and IL-6) in parallel to diminished PL expression and secretion (in vitro and ex vivo models). Irisin addition up-regulated the expression of pro-survival UPR markers (ATF6 and XBP-1) and reduced UPR pro-apoptotic markers (CHOP) under cer-pancreatitis and induced ER stress (tunicamycin), consequently increasing cells viability. Irisin’s pro-survival effect under cer-pancreatitis state was abolished under PPARγ inhibition. Our findings suggest irisin as a potential therapeutic option for AP via its ability to up-regulate pro-survival UPR signals and activate the PPARγ-PGC1α-FNDC5 pathway.

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Section: Discussionmentioning

confidence: 99%

Irisin Ameliorate Acute Pancreatitis and Acinar Cell Viability through Modulation of the Unfolded Protein Response (UPR) and PPARγ-PGC1α-FNDC5 Pathways

Horwitz,

Birk

2024

Biomolecules

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“…Caspase-3 (CASP3), a cytoplasmic protease, plays a crucial role in apoptosis [58]. Research has shown that CASP3 is involved in the cleavage of β-amyloid protein, as well as Tau protein and presenilin protein (PS1, PS2), which are closely associated with AD [59].…”

Section: Molecular Dynamics Simulation Of the Casp3-6-gingerol Complexmentioning

confidence: 99%

“…The MMP2-6-Gingerol complex exhibited stable hydrogen bonds (1-4) throughout the MD simulation, with a maximum of six hydrogen bonds (Figure 9D). These hydrogen Caspase-3 (CASP3), a cytoplasmic protease, plays a crucial role in apoptosis [58]. Research has shown that CASP3 is involved in the cleavage of β-amyloid protein, as well as Tau protein and presenilin protein (PS1, PS2), which are closely associated with AD [59].…”

Section: Molecular Dynamics Simulation Of the Mmp2-6-gingerol Complexmentioning

confidence: 99%

Screening of Active Substances Regulating Alzheimer’s Disease in Ginger and Visualization of the Effectiveness on 6-Gingerol Pathway Targets

Pan,

Li,

Zhao

et al. 2024

Foods

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Ginger has been reported to potentially treat Alzheimer’s disease (AD), but the specific compounds responsible for this biological function and their mechanisms are still unknown. In this study, a combination of network pharmacology, molecular docking, and dynamic simulation technology was used to screen active substances that regulate AD and explore their mechanisms. The TCMSP, GeneCards, OMIM, and DisGeNET databases were utilized to obtain 95 cross-targets related to ginger’s active ingredients and AD as key targets. A functional enrichment analysis revealed that the pathways in which ginger’s active substances may be involved in regulating AD include response to exogenous stimuli, response to oxidative stress, response to toxic substances, and lipid metabolism, among others. Furthermore, a drug-active ingredient–key target interaction network diagram was constructed, highlighting that 6-Gingerol is associated with 16 key targets. Additionally, a protein–protein interaction (PPI) network was mapped for the key targets, and HUB genes (ALB, ACTB, GAPDH, CASP3, and CAT) were identified. Based on the results of network pharmacology and cell experiments, 6-Gingerol was selected as the active ingredient for further investigation. Molecular docking was performed between 6-Gingerol and its 16 key targets, and the top three proteins with the strongest binding affinities (ACHE, MMP2, and PTGS2) were chosen for molecular dynamics analysis together with the CASP3 protein as the HUB gene. The findings indicate that 6-Gingerol exhibits strong binding ability to these disease targets, suggesting its potential role in regulating AD at the molecular level, as well as in abnormal cholinesterase metabolism and cell apoptosis, among other related regulatory pathways. These results provide a solid theoretical foundation for future in vitro experiments using actual cells and animal experiments to further investigate the application of 6-Gingerol.

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“…Irisin, by enhancing insulin sensitivity and promoting energy expenditure, could help improve these metabolic issues; 3 , 6 Anti-inflammatory Action, chronic inflammation in individuals with HIV is associated with an increased risk of non-infectious diseases such as cardiovascular and liver diseases. The anti-inflammatory properties of irisin could help mitigate chronic inflammation, thereby reducing the risk of these complications; 7 , 8 Immune Function Modulation, HIV primarily damages the immune system by destroying CD4+ T cells. Irisin might indirectly affect immune regulation and has the potential to improve or support the immune status of individuals with HIV; 5 Promotion of Muscle Function and Reduction of Wasting Symptoms, individuals with HIV may experience muscle wasting and a decline in strength.…”

Section: Irisin Tregs and Aidsmentioning

confidence: 99%

“…Irisin is a glycosylated type I membrane protein, a cleavage product of fibronectin type III domain-containing protein 5 (FNDC5), and is highly homologous between humans and mice. 1–4 Recent studies have shown that irisin plays a significant role under various physiological and pathological conditions, including promoting bone remodeling, 5 improving the prognosis of metabolic diseases, 3 , 6 and exhibiting anti-inflammatory, 7 , 8 anti-oxidative stress, anti-apoptotic, 5 , 6 , 9 neuroprotective, 7 , 10 and organ ischemia-injury protective effects. 9 Multiple studies have indicated that irisin can enhance the function of natural killer cells and play various roles in immune regulation.…”

Section: Introductionmentioning

confidence: 99%

The Application Potential of the Regulation of Tregs Function by Irisin in the Prevention and Treatment of Immune-Related Diseases

Wang,

Xu,

et al. 2024

DDDT

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Irisin is a muscle factor induced by exercise, generated through the proteolytic cleavage of the membrane protein fibronectin type III domain-containing protein 5 (FNDC-5). Numerous studies have shown that irisin plays a significant role in regulating glucose and lipid metabolism, inhibiting oxidative stress, reducing systemic inflammatory responses, and providing neuroprotection. Additionally, irisin can exert immunomodulatory functions by regulating regulatory T cells (Tregs). Tregs are a highly differentiated subset of mature T cells that play a key role in maintaining self-immune homeostasis and are closely related to infections, inflammation, immune-related diseases, and tumors. Irisin exerts persistent positive effects on Treg cell functions through various mechanisms, including regulating Treg cell differentiation and proliferation, improving their function, modulating the balance of immune cells, increasing the production of anti-inflammatory cytokines, and enhancing metabolic functions, thereby helping to maintain immune homeostasis and prevent immune-related diseases. As an important myokine, irisin interacts with receptors on the cell membrane, activating multiple intracellular signaling pathways to regulate cell metabolism, proliferation, and function. Although the specific receptor for irisin has not been fully identified, integrins are considered potential receptors. Irisin activates various signaling pathways, including AMPK, MAPK, and PI3K/Akt, through integrin receptors, thereby exerting multiple biological effects. These research findings provide important clues for understanding the mechanisms of irisin’s action and theoretical basis for its potential applications in metabolic diseases and immunomodulation. This article reviews the relationship between irisin and Tregs, as well as the research progress of irisin in immune-related diseases such as multiple sclerosis, myasthenia gravis, acquired immune deficiency syndrome, type 1 diabetes, sepsis, and rheumatoid arthritis. Studies have revealed that irisin plays an important role in immune regulation by improving the function of Tregs, suggesting its potential application value in the treatment of immune-related diseases.

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FNDC5/Irisin protects neurons through Caspase3 and Bax pathways

Cited by 3 publications

References 47 publications

Irisin Ameliorate Acute Pancreatitis and Acinar Cell Viability through Modulation of the Unfolded Protein Response (UPR) and PPARγ-PGC1α-FNDC5 Pathways

Irisin Ameliorate Acute Pancreatitis and Acinar Cell Viability through Modulation of the Unfolded Protein Response (UPR) and PPARγ-PGC1α-FNDC5 Pathways

Screening of Active Substances Regulating Alzheimer’s Disease in Ginger and Visualization of the Effectiveness on 6-Gingerol Pathway Targets

The Application Potential of the Regulation of Tregs Function by Irisin in the Prevention and Treatment of Immune-Related Diseases

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