FDA-approved Secukinumab alleviates glial activation and immune cell infiltration in MPTP-induced mouse model of Parkinson's disease

Research overview

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Abstract Background: The negative role of interleukin-IL-17A (IL-17A) in neurodegeneration diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) has been investigated. The effect of FDA-approval Secukinumab (SEC), which selectively targets IL‐17A, on the modification of PD remains unclear. This study investigated the protective effect of SEC in MPTP mice and explored its potential mechanism. Methods: We explored the neuroprotective effect of SEC by evaluating the loss of dopaminergic neurons, the activation of glial cells and the infiltration of immune cells in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Results: We found that the treatment of SEC alleviated the loss of dopaminergic neurons and reversed behavioral deficits in MPTP mice. SEC treatment reduced the infiltration of peripheral leukocytes into the brain, especially CD4+T cells, NK cells and monocyte-macrophages, attenuated the activation of glial cells and the expression of pro-inflammatory cytokines in MPTP mice. In addition, we found that the release of corresponding chemokines (CCL2, CXCL9), which recruit peripheral immune cells into the brain, was reduced. Conclusion: These results suggest that Secukinumab protects dopaminergic neurons and attenuates neuroinflammation in MPTP-induced model. SEC treatment in PD might be an effective therapeutic approach for clinical application in the future.

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