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SP1-Driven FOXM1 Upregulation Induces Dopaminergic Neuron Injury in Parkinson’s Disease

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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.

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Data Availability

The data supporting this study’s findings are available on request from the corresponding author.

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  1. Department 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

    Li Dong & Lianbo Gao

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LD and LG wrote the paper and conceived and designed the experiments. LD and LG analyzed the data. LD and LG collected and provided the sample for this study. All authors have read and approved the final submitted manuscript.

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Correspondence to Li Dong.

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Dong, L., Gao, L. SP1-Driven FOXM1 Upregulation Induces Dopaminergic Neuron Injury in Parkinson’s Disease. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-023-03854-2

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