Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by impaired motor symptoms induced by the degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNc). Many factors are speculated to operate in the mechanism of PD, including oxidative stress, mitochondrial dysfunction, abnormal protein handling, and PD induced apoptosis. Besides, researchers have recently shown that inflammatory secretions may engage neighboring cells such as astrocytes, which then induce autocrine and paracrine responses that amplify the inflammation, leading to neurodegeneration. In the present study, we analyzed the neuroprotective and anti-inflammatory effects of collapsin response mediator protein 4 (CRMP4) deletion in 6-hydroxydopamine (6-OHDA)-injected male mice, as well as its effects on motor impairments. Our findings indicated that the deletion of CRMP4 could maintain the TH-positive fibers in the striatum and the TH-positive cells in SNc, attenuate the inflammatory responses, and improve motor coordination and rotational behavior. Furthermore, based on our findings at the early time points, we hypothesized that primary differences between the Crmp4+/+ and Crmp4−/− mice may occur in microglia instead of neurons. Although further work should be carried out to clarify the specific role of CRMP4 in the pathogenesis of PD, our findings suggest that it could be a possible target for the treatment of PD.

帕金森病 (PD) 是一种慢性神经退行性疾病，其特征是由黑质致密部 (SNc) 多巴胺能神经元变性引起的运动症状受损。据推测，PD 的发病机制中有许多因素，包括氧化应激、线粒体功能障碍、蛋白质处理异常和 PD 诱导的细胞凋亡。此外，研究人员最近表明，炎症分泌物可能会影响星形胶质细胞等邻近细胞，然后诱导自分泌和旁分泌反应，从而放大炎症，导致神经退行性变。在本研究中，我们分析了崩溃素反应介导蛋白 4 (CRMP4) 缺失对注射 6-羟基多巴胺 (6-OHDA) 的雄性小鼠的神经保护和抗炎作用，及其对运动障碍的影响。我们的研究结果表明，CRMP4 的缺失可以维持纹状体中的 TH 阳性纤维和 SNc 中的 TH 阳性细胞，减弱炎症反应，并改善运动协调和旋转行为。此外，根据我们在早期时间点的发现，我们假设Crmp4 +/+ 和Crmp4 -/− 小鼠之间的主要差异可能发生在小胶质细胞而不是神经元中。尽管需要开展进一步的工作来阐明 CRMP4 在 PD 发病机制中的具体作用，但我们的研究结果表明它可能是治疗 PD 的一个可能靶点。