Comparative transcriptome analysis in monocyte-derived macrophages of asymptomatic GBA mutation carriers and patients with GBA-associated Parkinson’s disease. Comparative transcriptome analysis in monocyte-derived macrophages of asymptomatic GBA mutation carriers and patients with GBA-associated Parkinson’s disease

We compared transcriptome of monocyte-derived macrophages of 5 patients with GBA-PD (4 L444P/N, 1 N370S/N) and 4 asymptomatic GBA mutation carriers (GBA-carriers) (3 L444P/N, 1 N370S/N) and 4 controls. We also conducted comparative transcriptome analysis for L444P/N only GBA-PD patients and GBA-carriers. Revealed deregulated genes in GBA-PD independently of GBA mutations (L444P or N370S) were involved in immune response, neuronal function. We found upregulated pathway associated with zinc metabolism in L444P/N GBA-PD patients. The potential important role of DUSP1 in the pathogenesis of GBA-PD was suggested.

本研究对5例葡萄糖脑苷脂酶（GBA）相关帕金森病（GBA-PD）患者（4例为L444P/N基因型，1例为N370S/N基因型）、4例无症状GBA突变携带者（其中3例为L444P/N基因型，1例为N370S/N基因型）及4例健康对照者的单核细胞源性巨噬细胞（monocyte-derived macrophages）转录组（transcriptome）开展了比较分析。本研究同时针对仅携带L444P/N基因型的GBA-PD患者与GBA突变携带者进行了比较转录组分析。研究发现，与GBA突变类型（L444P或N370S）无关的GBA-PD失调基因，主要参与免疫应答与神经元功能相关的生物学过程。在L444P/N基因型GBA-PD患者中，检测到锌代谢相关通路出现上调。本研究提示双特异性磷酸酶1（DUSP1）在GBA-PD的发病机制中可能具有重要作用。