CircPRDM5-mediated regulation of miR-433-3p and HDAC6 in Parkinson's disease: a novel neuroprotective axis

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Май 21, 2025

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons, leading to motor and non-motor symptoms. Despite advances in PD research, molecular mechanisms underlying its pathogenesis remain incompletely understood. Recent studies have highlighted potential role circular RNAs (circRNAs) diseases. This study aims investigate regulatory circPRDM5 PD, focusing on interactions with miR-433-3p HDAC6. Bioinformatics tools were used identify interaction miR-433-3p. Peripheral blood samples collected from 20 patients healthy controls measure circPRDM5, miR-433-3p, HDAC6 expression. For vivo studies, an MPTP-induced mouse model was established, knockdown achieved via tail vein injections shRNA constructs. Behavioral tests, histological analysis, immunohistochemistry evaluate function neuronal integrity. In vitro, SH-SY5Y neuroblastoma cells treated MPP⁺ induce PD-like characteristics, followed transfection constructs mimics or inhibitors. Cell viability, lactate dehydrogenase (LDH) release, apoptosis, autophagy measured through CCK-8 assay, flow cytometry, western blotting, immunofluorescence. CircPRDM5 expression significantly elevated mice, alleviating deficits damage vivo. reduced MPP+-induced cellular damage, autophagy. analysis identified as target downregulation MPP+-treated observed. Dual-luciferase RNA pull-down assays confirmed that functions sponge for which regulates found be upregulated contributed damage. Furthermore, overexpression reversed protective effects knockdown, highlighting circPRDM5/miR-433-3p/HDAC6 axis pathology. reveals promotes sponging upregulating HDAC6, contributing apoptosis Knockdown reduces symptoms both animal models, providing therapeutic PD. Targeting may offer new opportunities disease-modifying treatments

Язык: Английский

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Targeting the bile acid receptor TGR5 with Gentiopicroside to activate Nrf2 antioxidant signaling and mitigate Parkinson’s disease in an MPTP mouse model

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by classical symptoms including bradykinesia, rest tremor and rigidity. Oxidative stress mitochondrial dysfunction are recognized as pivotal factors in PD progression. Gentiopicroside (GPS), secoiridoid derived from Gentiana manshurica Kitagawa, exhibits antioxidant mitophagy induction properties. Nonetheless, the effects mechanisms which GPS mitigates neurodegeneration remain to be thoroughly elucidated. The goal of this study was investigate neuroprotective models. We established MPTP/MPP+-induced models measure neuroprotection GPS. Transcriptomic analysis, oxidative biochemical kits, western blot cell immunofluorescence were conducted elucidate fundamental at play. Subsequently, targeting activation transmembrane G protein-coupled receptor-5 (TGR5) measured molecular docking, cellular thermal shift assay, microscale thermophoresis (MST) cyclic adenosine monophosphate (cAMP) quantitation. Finally, we verified whether dependent on TGR5 using specific small interfering RNA (siRNA), pharmacological antagonist knockout mice. significantly attenuated dopaminergic (DAergic) neuron loss restored motor function MPTP-induced mouse model. Whole-genome sequencing subsequent mechanistic investigations revealed that enhanced expression facilitated nuclear entry factor erythroid-related 2-factor 2 (Nrf2), reduced stimulated neurotoxin. Additionally, could target prevent its downregulation TGR5's silencing or inhibition weakened effect blocked GPS-mediated Nrf2 signaling Moreover, therapeutic mitigating deficits also abolished Tgr5 These findings collectively indicated targeted activate ultimately ameliorated pathological progression PD.

Язык: Английский

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Astragaloside IV ameliorates Parkinson's disease by inhibiting TLR4/NF-κB-dependent neuroinflammation

International Immunopharmacology, Год журнала: 2025, Номер 160, С. 114972 - 114972

Опубликована: Май 30, 2025

Язык: Английский

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The emerging role of circular RNAs in Parkinson’s disease

Frontiers in Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Фев. 16, 2023

Parkinson’s disease (PD) is the second most prevalent neurodegenerative and common movement disorder. It involves a gradual loss of dopaminergic neurons in substantia nigra. Although many studies have been conducted, underlying molecular pathways PD remain largely unknown. Circular RNAs (circRNAs), novel class non-coding with covalently closed loop structure, are brain. They stable, conserved molecules that widely expressed eukaryotes tissue-, cell-, development-specific patterns. Many circRNAs recently identified nervous system diseases, some circRNA expression profiles linked to PD. Given recent research has indicated essential roles various development progression identification individual may be promising strategy for finding new treatment targets Moreover, search high specificity sensitivity will open up avenues early diagnosis Herein, we address biogenesis, properties, review their potential utility as biomarkers therapeutic

Язык: Английский

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Protein-coding circular RNAs – mechanism, detection, and their role in cancer and neurodegenerative diseases

Biochemical and Biophysical Research Communications, Год журнала: 2023, Номер 678, С. 68 - 77

Опубликована: Авг. 18, 2023

Язык: Английский

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