目的  检测突触体相关蛋白25（SNAP25）的表达变化与肌萎缩侧索硬化症（ALS）发病的关系，探讨SNAP25对ALS运动神经元的保护作用，为ALS提供潜在的治疗靶点。方法  通过公共数据库筛选ALS转基因小鼠差异表达基因。聚焦SNAP25，选取36对不同发病时间点hSOD1-G93A突变型ALS转基因小鼠及同窝野生型（WT）小鼠作为动物模型，构建hSOD1-G93A突变型和hSOD1-WT NSC34细胞作为ALS细胞模型，通过Real-time PCR和Western blotting实验进行体内外差异表达验证。应用免疫荧光实验检测小鼠脊髓中SNAP25与神经元核抗原(NeuN)的共定位。过表达hSOD1-G93A突变型NSC34细胞中SNAP25，应用细胞活力试剂盒检测活力变化。诱导突起后分析突起生长的变化，同时检测βⅢ-tubulin和生长相关蛋白 43 (GAP-43)的表达。结果  公共数据库分析结果显示，SNAP25在ALS转基因小鼠脊髓中较WT组异常低表达。动物实验证实，相对于WT小鼠，ALS小鼠脊髓中SNAP25蛋白与mRNA水平均降低；SNAP25在小鼠脊髓中与NeuN共定位，ALS小鼠中SNAP25阳性神经元中SNAP25积分吸光度值下降。细胞实验发现，在hSOD1-G93A突变型 NSC34细胞中SNAP25蛋白及mRNA表达降低，过表达Snap25可提高细胞活力，促进神经突起生长。结论  SNAP25表达下调与ALS病理进程密切相关，上调Snap25可改善hSOD1-G93A 突变型NSC34细胞的存活状态，促进神经突起生长，发挥神经保护作用。

Objective  To investigate the relationship between the expression changes of synaptosomal-associated protein 25 (SNAP25) and the onset of amyotrophic lateral sclerosis (ALS), explore the neuroprotective effect of SNAP25 on ALS motor neurons, and provide potential therapeutic targets for ALS.  Methods  Differentially expressed genes in ALS transgenic mice were screened using public databases. Focusing on SNAP25, 36 pairs of hSOD1-G93A transgenic ALS mice and their wild-type (WT) littermates at different disease onset time points were selected as animal models. hSOD1-G93A mutant and hSOD1-WT NSC34 cells were generated as ALS cell models. Real-time PCR and Western blotting were used to verify differential expression in vivo and in vitro. Immunofluorescence assays were performed to detect the co-localization of SNAP25 with neuronal marker neuronal nuclei (NeuN) in mouse spinal cords. SNAP25 was overexpressed in hSOD1-G93A mutant NSC34 cells, and cell viability was measured using a cell viability assay kit. After neurite induction, changes in neurite growth were analyzed, along with the expression of neurite-related proteins βⅢ-tubulin and growth associated protein 43（GAP-43). Results  Analysis of public databases revealed that SNAP25 expression was significantly lower in the spinal cord of ALS transgenic mice compared to WT mice. Animal studies confirmed that, compared to WT mice, the levels of SNAP25 protein and mRNA in the spinal cord of ALS mice decreased; SNAP25 co-localized with NeuN in the mouse spinal cord, and the integrated optical density of SNAP25 in SNAP25-positive neurons in ALS mice decreased. In vitro experiments revealed that the expression levels of SNAP25 protein and mRNA in hSOD1-G93A mutant NSC34 cells were reduced, and overexpression of Snap25 improved cell viability and promoted neurite outgrowth. Conclusion  The down-regulation of SNAP25 expression is closely related to the pathological process of ALS. Overexpression of Snap25 enhances the viability of hSOD1-G93A mutant NSC34 cells, promotes neurite outgrowth, thereby exerting a neuroprotective effect.