miR-96-5p alleviates cerebral ischemia-reperfusion injury in mice by inhibiting pyroptosis via downregulating caspase 1

Experimental Neurology, Journal Year: 2024, Volume and Issue: 374, P. 114676 - 114676

Published: Jan. 6, 2024

Language: Английский

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Regulation of microglia polarization after cerebral ischemia

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: June 8, 2023

Stroke ranks second as a leading cause of death and permanent disability globally. Microglia, innate immune cells in the brain, respond rapidly to ischemic injury, triggering robust persistent neuroinflammatory reaction throughout disease’s progression. Neuroinflammation plays critical role mechanism secondary injury stroke is significant controllable factor. Microglia activation takes on two general phenotypes: pro-inflammatory M1 type anti-inflammatory M2 type, although reality more complex. The regulation microglia phenotype crucial controlling response. This review summarized key molecules mechanisms polarization, function, phenotypic transformation following cerebral ischemia, with focus influence autophagy polarization. goal provide reference for development new targets treatment based

Language: Английский

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Signaling pathways in brain ischemia: Mechanisms and therapeutic implications

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 251, P. 108541 - 108541

Published: Oct. 1, 2023

Language: Английский

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Knockdown of NEAT1 prevents post-stroke lipid droplet agglomeration in microglia by regulating autophagy

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Jan. 12, 2024

Abstract Background Lipid droplets (LD), lipid-storing organelles containing neutral lipids like glycerolipids and cholesterol, are increasingly accepted as hallmarks of inflammation. The nuclear paraspeckle assembly transcript 1 (NEAT1), a long non-coding RNA with over 200 nucleotides, exerts an indispensable impact on regulating both LD agglomeration autophagy in multiple neurological disorders. However, knowledge to how NEAT1 modulates the formation associated signaling pathways is limited. Methods In this study, primary microglia were isolated from newborn mice exposed oxygen-glucose-deprivation/reoxygenation (OGD/R). To further explore NEAT1-dependent mechanisms, antisense oligonucleotide (ASO) was adopted silence under vitro conditions. Studying interactions regard hypoxic conditions, inhibitor activator 3-methyladenine (3-MA) rapamycin (RAPA) used, respectively. preclinical stroke model, received intraventricular injections ASO or control vectors order yield knockdown. Analysis readout parameters included qRT-PCR, immunofluorescence, western blot assays, behavioral tests. Results Microglia OGD/R displayed temporal pattern expression, peaking at four hours hypoxia followed by six reoxygenation. After effectively silencing NEAT1, autophagy-related proteins significantly repressed microglia. Stimulating conditions means RAPA reversed downregulation perilipin 2 (PLIN2) expression. On contrary, application 3-MA promoted repression expression LD-associated protein PLIN2. Under vivo increased 24 h post-stroke. Knockdown alleviated inhibited autophagy, resulting improved cerebral perfusion, reduced brain injury recovery. Conclusion key player stimulation, knockdown provides promising therapeutic value against stroke. Graphical abstract

Language: Английский

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Role of Senescent Astrocytes in Health and Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8498 - 8498

Published: May 9, 2023

For many decades after their discovery, astrocytes, the abundant glial cells of brain, were believed to work as a glue, supporting structure and metabolic functions neurons. A revolution that started over 30 years ago revealed additional these cells, including neurogenesis, gliosecretion, glutamate homeostasis, assembly function synapses, neuronal metabolism with energy production, others. These properties have been confirmed, limited however, proliferating astrocytes. During aging or following severe brain stress lesions, astrocytes are converted into no-longer-proliferating, senescent forms, similar in morphology but profoundly modified functions. The changed specificity is largely due altered gene expression. ensuing effects include downregulation typical upregulation others, concerned neuroinflammation, release pro-inflammatory cytokines, dysfunction etc., specific senescence program. decrease support protection by induces development, vulnerable regions, toxicity together cognitive decline. Similar changes, ultimately reinforced astrocyte aging, also induced traumatic events molecules involved dynamic processes. Senescent play critical roles development diseases. first demonstration, obtained for Alzheimer’s disease less than 10 ago, contributed elimination previously predominant neuro-centric amyloid hypothesis. initial effects, operating considerable time before appearance known symptoms evolve severity up proliferation during final outcome. Involvement other neurodegenerative diseases cancer now intensely investigated.

Language: Английский

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HABP2 Encapsulated by Peripheral Blood-Derived Exosomes Suppresses Astrocyte Autophagy to Exacerbate Neuroinflammatory Injury in Mice with Ischemic Stroke

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(12), P. 2347 - 2361

Published: June 9, 2023

Exosomes are shown to be involved in the regulation of neuroinflammatory injury. The current study analyzed how peripheral blood-derived exosomes affected hyaluronan-binding protein 2 (HABP2) expression regulate injury after ischemic stroke (IS). An IS animal model was stimulated by middle cerebral artery occlusion (MCAO), followed injection lentivirus. Peripheral blood samples were collected from MCAO mice different treatments. infarction volume, astrocyte activation, and neuroinflammation observed TTC staining, immunofluorescence, ELISA, respectively. HABP2 highly expressed brain tissues mice. Also, an enhancement noted their exosomes, while loss promoted autophagy reduced release inflammatory factors as well apoptosis neuronal cells. PAR1 overexpression reversed effect on Additionally, agonist PI3K/AKT/mTOR pathway, SC79, could also reverse sh-PAR1 neuroinflammation. Mechanistically, enhanced activate thereby suppressing cell autophagy. Overall, can PAR1/PI3K/AKT/mTOR pathway reduce aggravate IS.

Language: Английский

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Melatonin Mitigates Acidosis-Induced Neuronal Damage by Up-Regulating Autophagy via the Transcription Factor EB

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1170 - 1170

Published: Jan. 29, 2025

Acidosis, a common feature of cerebral ischemia and hypoxia, results in neuronal damage death. This study aimed to investigate the protective effects mechanisms action melatonin against acidosis-induced damage. SH-SY5Y cells were exposed an acidic environment simulate acidosis, photothrombotic (PT) infarction model was used establish animal male C57/BL6J mice. Both vivo vitro studies demonstrated that acidosis increased cytoplasmic transcription factor EB (TFEB) levels, reduced nuclear TFEB suppressed autophagy, as evidenced by elevated p62 higher LC3-II/LC3-I ratio, decreased synapse-associated proteins (PSD-95 synaptophysin), apoptosis. In contrast, promoted translocation TFEB, enhanced reversed Moreover, role melatonin’s neuroprotective validated modulating translocation. conclusion, mitigates promoting thereby enhancing autophagy. These findings offer new insights into potential treatments for acidosis.

Language: Английский

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EIF4A3-Induced circ_0029941 Promotes Astrocyte Activation Through Enhancing Autophagy via miR-224-5p/NFAT5 Axis

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Language: Английский

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Enhancement of oligodendrocyte autophagy alleviates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion in rats

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 13(5), P. 2107 - 2123

Published: March 15, 2023

Cognitive impairment caused by chronic cerebral hypoperfusion (CCH) is associated with white matter injury (WMI), possibly through the alteration of autophagy. Here, autophagy-lysosomal pathway (ALP) dysfunction in (WM) and its relationship cognitive were investigated rats subjected to two vessel occlusion (2VO). The results showed that occurred 28th day after 2VO. Injury autophagy activation mature oligodendrocytes neuronal axons sequentially WM 3rd day. By 14th day, abnormal accumulation substrate, lysosomal dysfunction, mechanistic target rapamycin (MTOR) observed WM, paralleled oligodendrocyte death. This indicates was followed ALP inhibition or dysfunction. To enhanced systemic treatment overexpression Beclin1 (BECN1) reduced death, subsequently alleviated WMI CCH. These reveal early 2VO, which aggravation impairment. study highlights alleviating enhancing has benefits for recovery

Language: Английский

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Mechanistic Insights and Potential Therapeutic Approaches in PolyQ Diseases via Autophagy

Biomedicines, Journal Year: 2023, Volume and Issue: 11(1), P. 162 - 162

Published: Jan. 9, 2023

Polyglutamine diseases are a group of congenital neurodegenerative categorized with genomic abnormalities in the expansion CAG triplet repeats coding regions specific disease-related genes. Protein aggregates toxic hallmark for polyQ and initiate neuronal death. Autophagy is catabolic process that aids removal damaged organelles or protein aggregates, required to maintain cellular homeostasis has potential fight against diseases, but this pathway gets affected under diseased conditions, as there direct impact on autophagy-related gene expression. The increase accumulation autophagy vesicles reported was due an may have been decrease flux. These reports suggested contribution pathology regulation autophagy. It demonstrated various disease models upregulation by using modulators can enhance dissolution delay progression. In review, interaction analyzed, therapeutic approach inducing drugs established pathogenesis.

Language: Английский

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