Choi Ko-Eun, Kim Sang-Yeon, Jang Jinhee, Ryu Dong-Woo, Oh Yoonsang, Kim Joong-Seok
Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, Republic of Korea.
Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Mol Neurobiol. 2025 Apr;62(4):4591-4604. doi: 10.1007/s12035-024-04581-y. Epub 2024 Oct 29.
Although α-synucleinopathy has been confirmed in the submandibular gland (SMG) tissue of Parkinson's disease (PD) patients, in-depth disease-related molecular research, such as tissue-specific transcriptional signals, has not been performed. In the present study, disease-relevant tissue-specific transcriptional signals in SMG tissue from PD patients were investigated to identify potential diagnostic, prognostic, and pathophysiologic biomarkers. Here, seven de novo drug-naïve PD patients and six age- and sex-matched individuals without neurological or psychological diseases were enrolled. Total RNA sequencing (RNA-seq) and total small RNA-seq (smRNA-seq) were performed on SMG tissue and blood samples, with 26 RNA-seq and 26 smRNA-seq samples used for the final analysis. Differentially expressed genes (DEGs) and microRNAs in SMG tissue and blood from PD patients were obtained and their functional integration and interaction network were analyzed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the DEGs interacted with cytokine-, inflammation-, and immune-related pathways. Synphilin-1 expression was significantly downregulated in SMG tissue of PD patients, and α-synuclein expression did not significantly differ between PD patients and controls in either SMG tissue or blood. Fifteen tissue-specific miRNA signals in SMG tissue were identified that showed better diagnostic ability compared with those in blood samples. The correlation between DEGs and environmental factors appeared altered in PD patients. The results indicated the DEGs and microRNA signatures identified in SMG tissue may be promising diagnostic and prognostic biomarkers. These molecular insights offer potential avenues for the development of novel therapeutic strategies targeting the underlying disease mechanisms in PD patients.
尽管在帕金森病（PD）患者的下颌下腺（SMG）组织中已证实存在α-突触核蛋白病，但尚未进行深入的疾病相关分子研究，如组织特异性转录信号研究。在本研究中，对PD患者SMG组织中与疾病相关的组织特异性转录信号进行了研究，以确定潜在的诊断、预后和病理生理生物标志物。在此，招募了7例初发未用药的PD患者和6例年龄及性别匹配、无神经或心理疾病的个体。对SMG组织和血液样本进行了全RNA测序（RNA-seq）和全小RNA测序（smRNA-seq），最终分析使用了26个RNA-seq样本和26个smRNA-seq样本。获得了PD患者SMG组织和血液中差异表达基因（DEGs）和微小RNA，并分析了它们的功能整合和相互作用网络。京都基因与基因组百科全书（KEGG）通路分析显示，DEGs与细胞因子、炎症和免疫相关通路相互作用。在PD患者的SMG组织中，Synphilin-1表达显著下调，在SMG组织或血液中，PD患者与对照组之间的α-突触核蛋白表达无显著差异。在SMG组织中鉴定出15个组织特异性miRNA信号，与血液样本相比，其诊断能力更强。在PD患者中，DEGs与环境因素之间的相关性似乎发生了改变。结果表明，在SMG组织中鉴定出的DEGs和微小RNA特征可能是有前景的诊断和预后生物标志物。这些分子见解为开发针对PD患者潜在疾病机制的新型治疗策略提供了潜在途径。
