Targeting autophagy in ischemic stroke: From molecular mechanisms to clinical therapeutics

Pharmacology & Therapeutics, Journal Year: 2021, Volume and Issue: 225, P. 107848 - 107848

Published: April 4, 2021

Language: Английский

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A novel mechanism linking ferroptosis and endoplasmic reticulum stress via the circPtpn14/miR-351-5p/5-LOX signaling in melatonin-mediated treatment of traumatic brain injury

Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 178, P. 271 - 294

Published: Dec. 6, 2021

Traumatic brain injury (TBI) can lead to disability or devastating consequences with few established treatments. Although ferroptosis has been shown be involved in TBI, the underlying mechanism was rarely known. Melatonin indicated exhibit neuroprotective activities. However, anti-ferroptotic effects of melatonin on TBI have not yet elucidated. We aimed investigate whether induced humans after and inhibition by could protect against blood-brain barrier (BBB) damage vivo vitro. Circular RNAs (circRNAs) are highly expressed brain. For first time, differentially circRNA treatment for were detected RNA sequencing. found that lipid peroxidation while significantly improved function mice alleviated endoplasmic reticulum (ER) stress A total 1826 circRNAs (fold change >2, Q < 0.01), including 921 down-regulated 905 up-regulated injured tissues receiving treatment. Mechanistically, administration reduced level circPtpn14 (mmu_circ_0000130), which functioned acting as a miR-351-5p sponge positively regulate expression ferroptosis-related 5-lipoxygenase (5-LOX). Moreover, overexpression partly abolished inhibitory ferroptosis. Collectively, our findings provide evidence exert anti-ER alleviating via circPtpn14/miR-351-5p/5-LOX signaling.

Language: Английский

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The influence of circular RNAs on autophagy and disease progression

Autophagy, Journal Year: 2021, Volume and Issue: 18(2), P. 240 - 253

Published: April 27, 2021

Circular RNAs (circRNAs) are non-coding that have attracted considerable attention in recent years. Owing to their distinct circular structure, circRNAs stable cells. Autophagy is a catabolic process helps the degradation and recycling of harmful or inessential biological macromolecules cells enables adapt stress changes internal external environments. Evidence has shown influence course disease by regulating autophagy, which indicates autophagy involved onset development various diseases can affect drug resistance (for example, it affects cisplatin tumors). In this review, we summarized role on progression as well resistance. The review will expand our understanding tumors cardiovascular neurological also suggest novel therapeutic strategies.Abbreviations: ACR: autophagy-related circRNA; ADSCs: adipogenic mesenchymal stem cells; AMPK: AMP-activated protein kinase; ATG: related; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; ceRNA: competing endogenous RNA; circRNA: CMA: chaperone-mediated autophagy; EPCs: endothelial progenitor LE/MVBs: late endosomes/multivesicular bodies; MAP1LC3/LC3: microtubule associated 1 light chain 3; MTOR: mechanistic target rapamycin NSCLC: non-small cell lung cancer; PDLSCs: periodontal ligament PE: phosphatidylethanolamine; PtdIns: phosphatidylinositol; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate 1,2-dipalmitoyl; PTEN: phosphatase tensin homolog; RBPs: RNA-binding proteins; SiO2: silicon dioxide; TFEB: transcription factor EB; ULK: unc-51 like activating kinase 1.

Language: Английский

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The neuroprotective effect of dexmedetomidine and its mechanism

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 20, 2022

Dexmedetomidine (DEX) is a highly selective α2 receptor agonist that routinely used in the clinic for sedation and anesthesia. Recently, an increasing number of studies have shown DEX has protective effect against brain injury caused by traumatic (TBI), subarachnoid hemorrhage (SAH), cerebral ischemia ischemia-reperfusion (I/R), suggesting its potential as neuroprotective agent. Here, we summarized effects several models neurological damage examined mechanism based on current literature. Ultimately, found mainly involved inhibition inflammatory reactions, reduction apoptosis autophagy, protection blood-brain barrier enhancement stable cell structures five way. Therefore, can provide crucial advantage recovery patients with injury. The purpose this study was to further clarify mechanisms therefore clinical management injuries.

Language: Английский

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Combination therapies and other therapeutic approaches targeting the NLRP3 inflammasome and neuroinflammatory pathways: a promising approach for traumatic brain injury

Immunopharmacology and Immunotoxicology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 17

Published: Jan. 6, 2025

Objectives: Traumatic brain injury (TBI) precipitates a neuroinflammatory cascade, with the NLRP3 inflammasome emerging as critical mediator. This review scrutinizes complex activation pathways of by underscoring intricate interplay between calcium signaling, mitochondrial disturbances, redox imbalances, lysosomal integrity, and autophagy. It is hypothesized that combination therapy approach—integrating NF-κB pathway inhibitors antagonists—holds potential to synergistically dampen inflammatory storm associated TBI.

Language: Английский

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Insights into the multifaceted role of circular RNAs: implications for Parkinson’s disease pathogenesis and diagnosis

npj Parkinson s Disease, Journal Year: 2022, Volume and Issue: 8(1)

Published: Jan. 10, 2022

Parkinson's disease (PD) is a complex, age-related, neurodegenerative whose etiology, pathology, and clinical manifestations remain incompletely understood. As result, care focuses primarily on symptoms relief. Circular RNAs (circRNAs) are large class of mostly noncoding that accumulate with aging in the brain increasingly shown to regulate all aspects neuronal glial development function. They generated by spliceosome through backsplicing linear RNA. Although their biological role remains largely unknown, they have been transcription splicing, act as decoys for microRNAs RNA binding proteins, used templates translation, serve scaffolding platforms signaling components. Considering stable, diverse, detectable easily accessible biofluids, deemed promising biomarkers diagnosing diseases. CircRNAs differentially expressed patients PD, growing evidence suggests PD pathogenetic processes. Here, biogenesis, expression, degradation, detection circRNAs, well proposed functions, reviewed. Thereafter, research linking circRNAs PD-related processes, including aging, alpha-synuclein dysregulation, neuroinflammation, oxidative stress highlighted, followed recent use prognostic diagnostic PD.

Language: Английский

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Autophagy and Apoptosis in Acute Brain Injuries: From Mechanism to Treatment

Antioxidants and Redox Signaling, Journal Year: 2022, Volume and Issue: 38(1-3), P. 234 - 257

Published: May 17, 2022

Significance: Autophagy and apoptosis are two important cellular mechanisms behind brain injuries, which severe clinical situations with increasing incidences worldwide. To search for more better treatments it is essential to deepen the understanding of autophagy, apoptosis, their interactions in injuries. This article first analyzes how autophagy participate pathogenetic processes injuries respectively mutually, then summarizes some promising targeting show potential applications personalized medicine precision future. Recent Advances: Most current studies suggest that detrimental recovery. Several indicate can cause unnecessary death neurons after while others beneficial acute (ABIs) by facilitating removal damaged proteins organelles. Whether or ABIs depends on many factors, results from different research groups diverse even controversial, making this topic appealing be explored further. Critical Issues: Neuronal primary pathological ABIs. How they interact each other regulations affect outcome prognosis remain uncertain, these answers critical. Future Directions: Insights into interplay between accurate balance may promote precise field Antioxid. Redox Signal. 38, 234–257.

Language: Английский

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Omega-3 polyunsaturated fatty acids alleviate early brain injury after traumatic brain injury by inhibiting neuroinflammation and necroptosis

Translational Neuroscience, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 1, 2023

Presently, traumatic brain injury (TBI) is a leading contributor to disability and mortality that places considerable financial burden on countries all over the world. Docosahexaenoic acid eicosapentaenoic are two kinds of omega-3 polyunsaturated fatty acids (ω-3 PUFA), both which have been shown beneficial biologically active anti-inflammatory antioxidant effects. However, neuroprotective effect ω-3 PUFA in TBI has not proven, its probable mechanism remains obscure. We suppose can alleviate early (EBI) via regulating necroptosis neuroinflammation after TBI. This research intended examine possible molecular pathways C57BL/6 mice model EBI caused by Cognitive function was assessed measuring neuronal necroptosis, neuroinflammatory cytokine levels, water content, neurological score. The findings demonstrate administration remarkably elevated scores, alleviated cerebral edema, reduced inflammatory levels NF-κB, interleukin-1β (IL-1β), IL-6, TNF-α, illustrating attenuated neuroinflammation, cell death following PPARγ/NF-κB signaling pathway partially responsible for activity ω-3. Collectively, our illustrate against necroptosis.

Language: Английский

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Circular RNA METTL9 contributes to neuroinflammation following traumatic brain injury by complexing with astrocytic SND1

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Feb. 17, 2023

Circular RNAs (circRNAs) are highly enriched in the central nervous system and have been implicated neurodegenerative diseases. However, whether how circRNAs contribute to pathological processes induced by traumatic brain injury (TBI) has not fully elucidated.We conducted a high-throughput RNA sequencing screen for well-conserved, differentially expressed cortex of rats subjected experimental TBI. METTL9 (circMETTL9) was ultimately identified as upregulated post-TBI further characterized RT-PCR agarose gel electrophoresis, Sanger sequencing, RNase R treatment. To examine potential involvement circMETTL9 neurodegeneration loss function following TBI, expression knocked-down microinjection shcircMETTL9 adeno-associated virus. Neurological functions were evaluated control, TBI-KD using modified neurological severity score, cognitive Morris water maze test, nerve cell apoptosis rate TUNEL staining. Pull-down assays mass spectrometry identify circMETTL9-binding proteins. Co-localization SND1 astrocytes examined fluorescence situ hybridization immunofluorescence double Changes levels chemokines estimated quantitative PCR western blotting.CircMETTL9 significantly peaked at 7 d cerebral TBI model rats, it abundantly astrocytes. We found that knockdown attenuated dysfunction, impairment, CircMETTL9 directly bound increased astrocytes, leading upregulation CCL2, CXCL1, CCL3, CXCL3, CXCL10, enhanced neuroinflammation.Altogether, we first propose is master regulator neuroinflammation thus major contributor dysfunction.

Language: Английский

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Noncoding RNA crosstalk in brain health and diseases

Neurochemistry International, Journal Year: 2021, Volume and Issue: 149, P. 105139 - 105139

Published: July 16, 2021

Language: Английский

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