Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Department of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan.
Mol Neurobiol. 2018 Aug;55(8):6319-6328. doi: 10.1007/s12035-017-0845-3. Epub 2018 Jan 2.
The pathogenesis of Parkinson's disease (PD) remains to be elucidated. Metabolomic analysis has the potential to identify biochemical pathways and metabolic profiles that are involved in PD pathogenesis. Here, we performed a targeted metabolomics to quantify the plasma levels of 184 metabolites in a discovery cohort including 82 PD patients and 82 normal controls (NCs) and found two up-regulated (dopamine, putrescine/ornithine ratio) and four down-regulated (octadecadienylcarnitine C18:2, asymmetric dimethylarginine, tryptophan, and kynurenine (KYN)) metabolites in the plasma of PD patients. We then measured the plasma levels of a panel of metabolic products of KYN pathway in an independent validation cohort including 118 PD patients, 22 Huntington's disease (HD) patients, and 37 NCs. Lower kynurenic acid (KA)/KYN ratio, higher quinolinic acid (QA) level, and QA/KA ratio were observed in PD patients compared to HD patients and NCs. PD patients at advanced stage (Hoehn-Yahr stage > 2) showed lower KA and KA/KYN ratio, as well as higher QA and QA/KA ratio compared to PD patients at early stage (Hoehn-Yahr stage ≤ 2) and NCs. Levels of KA and QA, as well as the ratios of KA/KYN and QA/KA between PD patients with and without psychiatric symptoms, dementia, or levodopa-induced dyskinesia in the advanced PD were similar. This metabolomic analyses demonstrate a number of plasma biomarker candidates for PD, suggesting a shift toward neurotoxic QA synthesis and away from neuroprotective KA production in KYN pathway.
帕金森病（PD）的发病机制仍有待阐明。代谢组学分析有可能确定涉及 PD 发病机制的生化途径和代谢特征。在这里，我们对包括 82 名 PD 患者和 82 名正常对照（NC）在内的发现队列进行了靶向代谢组学分析，以定量检测血浆中 184 种代谢物的水平，结果发现 PD 患者的血浆中存在两种上调的代谢物（多巴胺，腐胺/精氨酸比）和四种下调的代谢物（十八碳二烯基肉碱 C18:2、不对称二甲基精氨酸、色氨酸和犬尿氨酸（KYN））。然后，我们在一个独立的验证队列中测量了 KYN 途径的一组代谢产物的血浆水平，该队列包括 118 名 PD 患者、22 名亨廷顿病（HD）患者和 37 名 NC。与 HD 患者和 NC 相比，PD 患者的犬尿氨酸酸（KA）/KYN 比值较低，喹啉酸（QA）水平较高，QA/KA 比值较高。与早期（Hoehn-Yahr 分期≤2）PD 患者和 NC 相比，晚期（Hoehn-Yahr 分期>2）PD 患者的 KA 和 KA/KYN 比值较低，QA 和 QA/KA 比值较高。晚期 PD 患者伴有或不伴有精神症状、痴呆或左旋多巴诱导的运动障碍的 KA 和 QA 水平以及 KA/KYN 和 QA/KA 比值之间无差异。这项代谢组学分析为 PD 提供了一些潜在的血浆生物标志物候选物，表明 KYN 途径中的神经毒性 QA 合成增加，而神经保护 KA 生成减少。
