Background

Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by the degeneration and death of upper (UMN) and lower (LMN) motor neurons. In the last decade, it has been shown that Chitinases are an important prognostic indicator of neuro-inflammatory damage induced by microglia and astrocytes.

Materials and methods

We analyzed microarray datasets obtained from the Array Express in order to verify the expression levels of CHI3L1 and CHI3L2 in motor cortex biopsies of sALS patients with different survival times. We also divided the sALS patients into smokers and non-smokers. In order to extend our analysis, we explored two additional microarray datasets, GSE833 and GSE26927, of post-mortem spinal cord biopsies from sALS patients.

Results

The analysis showed that CHI3L1 and CHI3L2 expression levels were significantly upregulated in the motor cortex of sALS patients, compared to the healthy controls. Moreover, their expression levels were negatively correlated with survival time. Interesting results were obtained when we compared the expression levels of Chitinases among smokers. We showed that CHI3L1 and CHI3L2 were significantly upregulated in sALS smokers compared to non-smokers. Furthermore, we found that four genes belonging to the Chitinases network (SERPINA3, C1s, RRAD, HLA-DQA1) were significantly upregulated in the motor cortex of sALS patients and positively correlated with Chitinases expression levels. Similar results were obtained during the exploration of the two-microarray dataset.

Conclusions

This study suggests that CHI3L1 and CHI3L2 are associated with the progression of neurodegeneration in motor cortex and spinal cord of sALS patients.

中文翻译：

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CHI3L1和CHI3L2表达在运动皮质和脊髓SALS患者

背景

肌萎缩性侧索硬化症（ALS）是一种快速进行性神经退行性疾病，其特征在于上部（UMN）和下部（LMN）运动神经元的变性和死亡。在过去的十年中，已证明几丁质酶是小胶质细胞和星形胶质细胞诱导的神经炎性损伤的重要预后指标。

材料和方法

我们分析了从Array Express获得的微阵列数据集，以验证CHI3L1和CHI3L2在不同存活时间的sALS患者运动皮层活检中的表达水平。我们还将sALS患者分为吸烟者和非吸烟者。为了扩展我们的分析，我们探索了来自sALS患者的死后脊髓活检组织的两个其他微阵列数据集，GSE833和GSE26927 。

结果

分析显示，与健康对照组相比，sALS患者运动皮层中的CHI3L1和CHI3L2表达水平显着上调。而且，它们的表达水平与存活时间负相关。当我们比较吸烟者中几丁质酶的表达水平时，获得了有趣的结果。我们显示，与不吸烟者相比，在sALS吸烟者中CHI3L1和CHI3L2显着上调。此外，我们发现属于几丁质酶网络的四个基因（SERPINA3，C1s，RRAD，HLA-DQA1）在大肠杆菌中显着上调。sALS患者的运动皮层与几丁质酶表达水平呈正相关。在探索两个微阵列数据集的过程中获得了相似的结果。

结论

这项研究表明CHI3L1和CHI3L2与sALS患者的运动皮层和脊髓神经变性的进展有关。