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Updated: Jul 6, 2025
Primary Culture of Mouse Dopaminergic Neurons
Published on: September 8, 2014
SP1-Driven FOXM1 Upregulation Induces Dopaminergic Neuron Injury in Parkinson's Disease
1Department of Neurology, The Fourth Affiliated Hospital of China Medical University, No. 4, Chongshan East Road, Huanggu District, Shenyang, 110032, Liaoning Province, People's Republic of China. ldong@cmu.edu.cn.
Abstract:
The aberrant expression of Forkhead box M1 (FOXM1) has been associated with the pathological processes of Parkinson's disease (PD), but the upstream and downstream regulators remain poorly understood. This study sought to examine the underlying mechanism of FOXM1 in dopaminergic neuron injury in PD. Bioinformatics analysis was conducted to pinpoint the differential expression of FOXM1, which was verified in the nigral tissues of rotenone-lesioned mice and dopaminergic neuron MN9D cells. Interactions among SP1, FOXM1, SNAI2, and CXCL12 were analyzed. To evaluate their effects on dopaminergic neuron injury, the lentiviral vector-mediated manipulation of FOXM1, SP1, and CXCL12 was introduced in rotenone-lesioned mice and MN9D cells. SP1, FOXM1, SNAI2, and CXCL12 abundant expression occurred in rotenone-lesioned mice and MN9D cells. Silencing of FOXM1 delayed the rotenone-induced dopaminergic neuron injury in vitro. Mechanistically, SP1 was an upstream transcription factor of FOXM1 and upregulated FOXM1 expression, leading to increased SNAI2 and CXCL12 expression. In vivo, data confirmed that SP1 promoted dopaminergic neuron injury by activating the FOXM1/SNAI2/CXCL12 axis. Our data indicate that SP1 silencing has neuroprotective effects on dopaminergic neurons, which is dependent upon the inactivated FOXM1/SNAI2/CXCL12 axis.
Insights
Parkinson's disease involves Forkhead box M1 (FOXM1) dysregulation. SP1 activates FOXM1, driving dopaminergic neuron injury via the SNAI2/CXCL12 pathway, suggesting SP1 silencing as a neuroprotective strategy.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Aberrant Forkhead box M1 (FOXM1) expression is linked to Parkinson's disease (PD) pathology.
- The upstream and downstream regulatory mechanisms of FOXM1 in PD remain unclear.
- Understanding these mechanisms is crucial for developing targeted therapies for dopaminergic neuron injury.
Purpose of the Study:
- To investigate the role and regulatory mechanism of FOXM1 in dopaminergic neuron injury in Parkinson's disease.
- To identify upstream regulators and downstream targets of FOXM1 in PD.
- To evaluate the therapeutic potential of targeting the SP1/FOXM1 axis.
Main Methods:
- Bioinformatics analysis to identify differential gene expression.
- Verification of FOXM1 expression in rotenone-induced Parkinson's disease models (mice and cell lines).
- Lentiviral vector-mediated manipulation of SP1, FOXM1, and CXCL12 to assess their effects on dopaminergic neuron injury.
Main Results:
- SP1, FOXM1, SNAI2, and CXCL12 were found to be highly expressed in PD models.
- FOXM1 silencing demonstrated neuroprotective effects against rotenone-induced injury in vitro.
- SP1 acts as an upstream regulator, upregulating FOXM1, which in turn increases SNAI2 and CXCL12 expression, promoting dopaminergic neuron injury.
Conclusions:
- SP1 promotes dopaminergic neuron injury in Parkinson's disease by activating the FOXM1/SNAI2/CXCL12 signaling axis.
- SP1 silencing exhibits neuroprotective effects in dopaminergic neurons.
- Inactivation of the FOXM1/SNAI2/CXCL12 axis via SP1 silencing offers a potential therapeutic strategy for Parkinson's disease.
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