CircPRDM5-mediated regulation of miR-433-3p and HDAC6 in Parkinson's disease: a novel neuroprotective axis
Abstract Background 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, the molecular mechanisms underlying its pathogenesis remain incompletely understo...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-025-06602-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849730804477853696 |
|---|---|
| author | Kai Wang Langfeng Zhu Zhibo Ren |
| author_facet | Kai Wang Langfeng Zhu Zhibo Ren |
| author_sort | Kai Wang |
| collection | DOAJ |
| description | Abstract Background 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, the molecular mechanisms underlying its pathogenesis remain incompletely understood. Recent studies have highlighted the potential role of circular RNAs (circRNAs) in neurodegenerative diseases. This study aims to investigate the regulatory role of circPRDM5 in PD, focusing on its interactions with miR-433-3p and HDAC6. Methods Bioinformatics tools were used to identify circPRDM5 and its potential interaction with miR-433-3p. Peripheral blood samples were collected from 20 PD patients and healthy controls to measure circPRDM5, miR-433-3p, and HDAC6 expression. For in vivo studies, an MPTP-induced PD mouse model was established, and circPRDM5 knockdown was achieved via tail vein injections of shRNA constructs. Behavioral tests, histological analysis, and immunohistochemistry were used to evaluate motor function and neuronal integrity. In vitro, SH-SY5Y neuroblastoma cells were treated with MPP⁺ to induce PD-like characteristics, followed by transfection with circPRDM5 knockdown constructs and miR-433-3p mimics or inhibitors. Cell viability, lactate dehydrogenase (LDH) release, apoptosis, and autophagy were measured through CCK-8 assay, flow cytometry, western blotting, and immunofluorescence. Results CircPRDM5 expression was significantly elevated in PD patients and MPTP-induced PD mice, with knockdown of circPRDM5 alleviating motor deficits and neuronal damage in vivo. In vitro, circPRDM5 knockdown in SH-SY5Y cells reduced MPP+-induced cellular damage, apoptosis, and autophagy. Bioinformatics analysis identified miR-433-3p as a target of circPRDM5, and its downregulation in PD patients and MPP+-treated cells was observed. Dual-luciferase and RNA pull-down assays confirmed that circPRDM5 functions as a sponge for miR-433-3p, which regulates HDAC6 expression. HDAC6 was found to be upregulated in PD and contributed to neuronal damage. Furthermore, HDAC6 overexpression reversed the protective effects of circPRDM5 knockdown, highlighting the role of the circPRDM5/miR-433-3p/HDAC6 axis in PD pathology. Conclusions This study reveals that circPRDM5 promotes neuronal damage in PD by sponging miR-433-3p and upregulating HDAC6, contributing to apoptosis and autophagy. Knockdown of circPRDM5 reduces PD-like symptoms in both cellular and animal models, providing a potential therapeutic target for PD. Targeting the circPRDM5/miR-433-3p/HDAC6 axis may offer new opportunities for disease-modifying treatments in PD. |
| format | Article |
| id | doaj-art-f4fdc2eed8124593aad0b0582a2e4e85 |
| institution | DOAJ |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-f4fdc2eed8124593aad0b0582a2e4e852025-08-20T03:08:44ZengBMCJournal of Translational Medicine1479-58762025-05-0123112010.1186/s12967-025-06602-3CircPRDM5-mediated regulation of miR-433-3p and HDAC6 in Parkinson's disease: a novel neuroprotective axisKai Wang0Langfeng Zhu1Zhibo Ren2Department of Pediatric Surgery, The Affiliated Hospital of Qingdao UniversityDepartment of Pediatric Surgery, General Hospital of Ningxia Medical UniversityDepartment of Pediatric Surgery, General Hospital of Ningxia Medical UniversityAbstract Background 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, the molecular mechanisms underlying its pathogenesis remain incompletely understood. Recent studies have highlighted the potential role of circular RNAs (circRNAs) in neurodegenerative diseases. This study aims to investigate the regulatory role of circPRDM5 in PD, focusing on its interactions with miR-433-3p and HDAC6. Methods Bioinformatics tools were used to identify circPRDM5 and its potential interaction with miR-433-3p. Peripheral blood samples were collected from 20 PD patients and healthy controls to measure circPRDM5, miR-433-3p, and HDAC6 expression. For in vivo studies, an MPTP-induced PD mouse model was established, and circPRDM5 knockdown was achieved via tail vein injections of shRNA constructs. Behavioral tests, histological analysis, and immunohistochemistry were used to evaluate motor function and neuronal integrity. In vitro, SH-SY5Y neuroblastoma cells were treated with MPP⁺ to induce PD-like characteristics, followed by transfection with circPRDM5 knockdown constructs and miR-433-3p mimics or inhibitors. Cell viability, lactate dehydrogenase (LDH) release, apoptosis, and autophagy were measured through CCK-8 assay, flow cytometry, western blotting, and immunofluorescence. Results CircPRDM5 expression was significantly elevated in PD patients and MPTP-induced PD mice, with knockdown of circPRDM5 alleviating motor deficits and neuronal damage in vivo. In vitro, circPRDM5 knockdown in SH-SY5Y cells reduced MPP+-induced cellular damage, apoptosis, and autophagy. Bioinformatics analysis identified miR-433-3p as a target of circPRDM5, and its downregulation in PD patients and MPP+-treated cells was observed. Dual-luciferase and RNA pull-down assays confirmed that circPRDM5 functions as a sponge for miR-433-3p, which regulates HDAC6 expression. HDAC6 was found to be upregulated in PD and contributed to neuronal damage. Furthermore, HDAC6 overexpression reversed the protective effects of circPRDM5 knockdown, highlighting the role of the circPRDM5/miR-433-3p/HDAC6 axis in PD pathology. Conclusions This study reveals that circPRDM5 promotes neuronal damage in PD by sponging miR-433-3p and upregulating HDAC6, contributing to apoptosis and autophagy. Knockdown of circPRDM5 reduces PD-like symptoms in both cellular and animal models, providing a potential therapeutic target for PD. Targeting the circPRDM5/miR-433-3p/HDAC6 axis may offer new opportunities for disease-modifying treatments in PD.https://doi.org/10.1186/s12967-025-06602-3Parkinson’s diseaseCircPRDM5MiR-433-3pHDAC6AutophagyApoptosis |
| spellingShingle | Kai Wang Langfeng Zhu Zhibo Ren CircPRDM5-mediated regulation of miR-433-3p and HDAC6 in Parkinson's disease: a novel neuroprotective axis Journal of Translational Medicine Parkinson’s disease CircPRDM5 MiR-433-3p HDAC6 Autophagy Apoptosis |
| title | CircPRDM5-mediated regulation of miR-433-3p and HDAC6 in Parkinson's disease: a novel neuroprotective axis |
| title_full | CircPRDM5-mediated regulation of miR-433-3p and HDAC6 in Parkinson's disease: a novel neuroprotective axis |
| title_fullStr | CircPRDM5-mediated regulation of miR-433-3p and HDAC6 in Parkinson's disease: a novel neuroprotective axis |
| title_full_unstemmed | CircPRDM5-mediated regulation of miR-433-3p and HDAC6 in Parkinson's disease: a novel neuroprotective axis |
| title_short | CircPRDM5-mediated regulation of miR-433-3p and HDAC6 in Parkinson's disease: a novel neuroprotective axis |
| title_sort | circprdm5 mediated regulation of mir 433 3p and hdac6 in parkinson s disease a novel neuroprotective axis |
| topic | Parkinson’s disease CircPRDM5 MiR-433-3p HDAC6 Autophagy Apoptosis |
| url | https://doi.org/10.1186/s12967-025-06602-3 |
| work_keys_str_mv | AT kaiwang circprdm5mediatedregulationofmir4333pandhdac6inparkinsonsdiseaseanovelneuroprotectiveaxis AT langfengzhu circprdm5mediatedregulationofmir4333pandhdac6inparkinsonsdiseaseanovelneuroprotectiveaxis AT zhiboren circprdm5mediatedregulationofmir4333pandhdac6inparkinsonsdiseaseanovelneuroprotectiveaxis |