DAPK1/MAPK1 Axis Regulates Neuronal Damage in Parkinson's Disease Models

Zhongkun REN; Bibo GAO; Xueling SUN; Lingying ZHU; Yinfang SU

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Zhongkun REN, Bibo GAO, Xueling SUN, Lingying ZHU, Yinfang SU. DAPK1/MAPK1 Axis Regulates Neuronal Damage in Parkinson's Disease Models[J]. Journal of Kunming Medical University.

Citation:

Zhongkun REN, Bibo GAO, Xueling SUN, Lingying ZHU, Yinfang SU. DAPK1/MAPK1 Axis Regulates Neuronal Damage in Parkinson's Disease Models[J]. Journal of Kunming Medical University.

Zhongkun REN, Bibo GAO, Xueling SUN, Lingying ZHU, Yinfang SU. DAPK1/MAPK1 Axis Regulates Neuronal Damage in Parkinson's Disease Models[J]. Journal of Kunming Medical University.

Citation:

Zhongkun REN, Bibo GAO, Xueling SUN, Lingying ZHU, Yinfang SU. DAPK1/MAPK1 Axis Regulates Neuronal Damage in Parkinson's Disease Models[J]. Journal of Kunming Medical University.

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DAPK1/MAPK1 Axis Regulates Neuronal Damage in Parkinson's Disease Models

1.
Department of Neurosurgery I，The First Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650032
2.
Project Management Department，Yunnan Yunke Biotechnology Research Institute，Kunming Yunnan 650503，China

Received Date: 2025-12-26
Available Online: 2026-03-20

Abstract

Abstract

Objective To elucidate the mechanism of the death-associated protein kinase 1 （DAPK1）/mitogen-activated protein kinase 1 （MAPK1） axis in the pathogenesis of Parkinson's disease （PD）. Methods In vivo and in vitro PD models were established using 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine （MPTP） and 1-methyl-4-phenylpyridinium （MPP⁺）, respectively. Plasmids encoding si-DAPK1 and oe-MAPK1 were transfected into cells, and transfection efficiency was assessed using RT-qPCR and Western blotting. Cell viability, apoptosis levels, caspase-3 and caspase-9 activities, and levels of lactate dehydrogenase （LDH）, superoxide dismutase （SOD）, reactive oxygen species （ROS）, tumor necrosis factor α （TNF-α）, interleukin 1β （IL-1β）, and interleukin 6 （IL-6） were assessed using CCK-8 assay, flow cytometry, commercial kits, and enzyme-linked immunosorbent assay （ELISA）. Protein-protein interactions were predicted using the STRING database and verified by co-immunoprecipitation （CO-IP）. Results DAPK1 and MAPK1 expression levels were significantly elevated in both in vivo and in vitro PD models. Silencing DAPK1 attenuated MPP⁺-induced apoptosis and reduced caspase-3 and caspase-9 levels in MN9D cells, decreased LDH, ROS, TNF-α, IL-1β, and IL-6 levels and increased SOD content. Direct interaction between DAPK1 and MAPK1 was demonstrated in cells. Overexpression of MAPK1 reversed the inhibitory effects of DAPK1 silencing promoted MPP⁺-induced neuroinflammation. Conclusion Silent DAPK1 exerts neuroprotective effects against MPP+-induced cytotoxicity through interaction with MAPK1, representing a potential therapeutic target for PD.
- Parkinson's disease,
- DAPK1,
- MAPK1,
- Apoptosis,
- Neuroinflammation

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References(33)

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