Dhiman Neetu Rani, Singh Surbhi, Singh Royana, Kumar Anand, Singh Varun Kumar, Pathak Abhishek, Chaurasia Rameshwar Nath, Mishra Vijay Nath, Srivastava Niraj Kumar, Sahu Swati, Pandey Nikhil, Joshi Deepika
Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
Front Bioinform. 2025 Mar 10;5:1513790. doi: 10.3389/fbinf.2025.1513790. eCollection 2025.
Parkinson's disease is a complex, age-related, neurodegenerative disease associated with dopamine deficiency and both motor and nonmotor deficits. Therapeutic pathways remain challenging in Parkinson's disease due to the low accuracy of early diagnosis, the difficulty in monitoring disease progression, and the limited availability of treatment options.
Few data are present to identify urinary biomarkers for various ailments, potentially aiding in the diagnosis and tracking of illness progression in individuals with Parkinson's disease. Thus, the analysis of urinary metabolomic biomarkers (UMB) for early and mid-stage idiopathic Parkinson's disease (IPD) is the main goal of this systematic review.
For this study, six electronic databases were searched for articles published up to 23 February 2024: PubMed, Ovid Medline, Embase, Scopus, Science Direct, and Cochrane. 5,377 articles were found and 40 articles were screened as per the eligibility criteria. Out of these, 7 controlled studies were selected for this review. Genetic profiling for gene function and biomarker interactions between urinary biomarkers was conducted using the STRING and Cytoscape database.
A total of 40 metabolites were identified to be related to the early and mid-stage of the disease pathology out of which three metabolites, acetyl phenylalanine (a subtype of phenylalanine), tyrosine and kynurenine were common and most significant in three studies. These metabolites cause impaired dopamine synthesis along with mitochondrial disturbances and brain energy metabolic disturbances which are considered responsible for neurodegenerative disorders. Furoglycine, Cortisol, Hydroxyphenylacetic acid, Glycine, Tiglyglycine, Aminobutyric acid, Hydroxyprogesterone, Phenylacetylglutamine, and Dihydrocortisol were also found commonly dysregulated in two of the total 7 studies. 158 genes were found which are responsible for the occurrence of PD and metabolic regulation of the corresponding biomarkers from our study.
The current review identified acetyl phenylalanine (a subtype of phenylalanine), tyrosine and kynurenine as potential urinary metabolomic biomarkers for diagnosing PD and identifying disease progression.
帕金森病是一种复杂的、与年龄相关的神经退行性疾病，与多巴胺缺乏以及运动和非运动功能障碍有关。由于早期诊断准确性低、监测疾病进展困难以及治疗选择有限，帕金森病的治疗途径仍然具有挑战性。
目前很少有数据可用于识别各种疾病的尿液生物标志物，这可能有助于帕金森病患者的疾病诊断和病情进展跟踪。因此，分析早期和中期特发性帕金森病（IPD）的尿液代谢组学生物标志物（UMB）是本系统评价的主要目标。
在本研究中，检索了六个电子数据库，以查找截至2024年2月23日发表 的文章：PubMed、Ovid Medline、Embase、Scopus、Science Direct和Cochrane。共找到5377篇文章，并根据纳入标准筛选出40篇文章。其中，7项对照研究被选入本评价。使用STRING和Cytoscape数据库对基因功能进行基因分型以及尿液生物标志物之间的生物标志物相互作用。
共鉴定出40种与疾病病理早期和中期相关的代谢物，其中三种代谢物，即乙酰苯丙氨酸（苯丙氨酸的一种亚型）、酪氨酸和犬尿氨酸在三项研究中是常见且最为显著的。这些代谢物会导致多巴胺合成受损以及线粒体紊乱和脑能量代谢紊乱，这些被认为是神经退行性疾病的原因。在总共7项研究中的两项中还发现，尿刊酸、皮质醇、对羟基苯乙酸、甘氨酸、惕各酰甘氨酸、氨基丁酸、羟孕酮、苯乙酰谷氨酰胺和双氢皮质醇也普遍失调。从我们的研究中发现了158个基因，它们与帕金森病的发生以及相应生物标志物的代谢调节有关。
本综述确定乙酰苯丙氨酸（苯丙氨酸的一种亚型）、酪氨酸和犬尿氨酸为诊断帕金森病和识别疾病进展的潜在尿液代谢组学生物标志物。
