EphA1 Activation Induces Neuropathological Changes in a Mouse Model of Parkinson's Disease Through the CXCL12/CXCR4 Signaling Pathway.

There is increasing evidence that EphA1 is involved in the function and development of the central nervous system, especially in neuroinflammation. It has been found to affect the disease progression of Alzheimer's disease (AD) by regulating the neuroinflammatory process. Neuroinflammation has always been regarded as the mechanism of the development of Parkinson's disease (PD) and possible therapeutic targets. Therefore, it is worth studying whether EphA1 has a potential therapeutic value for PD. The purpose of this study is to investigate the effect of EphA1 in mice and PD cell models and its mechanism.In this study, we verified the difference in expression of EphA1 and the effect and mechanism of EphA1 on neuropathological changes through Parkinson's patient samples, Parkinson's mice model, and Parkinson's model prepared from SH-SY5Y cells in vitro.EphA1 was highly expressed in the substantia nigra (SN) region of Parkinson mice and the Parkinson cell model, while the expression of tyrosine hydroxylase (TH) in the SN region of Parkinson mice was significantly reduced. After silenced EphA1 in the SH-SY5Y cell PD model, the expression levels of α-synuclein, inflammatory factors, and microglia-activated chemokine decreased. The co-immunoprecipitation experiment proved that EphA1 overexpression could promote the binding of CXCL12 and CXCR4. However, after silenced EphA1 and CXCL12 at the same time, the above effects brought by silenced EphA1 were suppressed. The same result appeared in mice with PD.EphA1 improves the inflammatory responses and neuropathological changes of the PD model in vivo and in vitro through the CXCL12/CXCR4 signaling pathway. Graphical abstract.