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探索潜在因果联系:帕金森病脑损伤如何影响肝脏健康——一项孟德尔随机化和转录组学研究

Exploring Potential Causal Links: How Parkinson's Disease Brain Damage Impacts Liver Health-A Mendelian Randomization and Transcriptomic Study.

作者信息

Liu Tingting, Chen Qi, Wu Haojie, Li Jingwen, Xian Meiyan, Lu Keke, Zhu Chaoyang, Wei Jianshe

机构信息

School of Life Sciences, Henan University, Kaifeng, People's Republic of China.

Translational Neuromedicine and Neurourology Center, Huaihe Hospital of Henan University, Kaifeng, People's Republic of China.

出版信息

J Inflamm Res. 2025 Jun 21;18:8173-8197. doi: 10.2147/JIR.S511645. eCollection 2025.

Abstract

BACKGROUND

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by slow movements, muscle rigidity, tremors, and changes in gait and posture. Clinical studies have demonstrated a close association between PD and liver disease, but most research has focused on the impact of liver disorders on brain damage in PD, and further exploration is needed to understand the pathways and mechanisms underlying liver damage in patients with PD.

METHODS

This study employs Mendelian Randomization (MR) and transcriptomic analysis to investigate the causal impact of PD-related brain damage on liver health, identifying serum metabolites (eg, cysteine) and shared immune-inflammatory pathways as mediators.

RESULTS

The study indicates that PD-related brain damage does indeed have an impact on liver metabolic function. PD-related brain damage may disrupt the concentration of cysteine, which, when elevated, can cause liver cell damage and oxidative stress. Additionally, PD-related brain damage may affect specific genes (such as NCF1, NCF, and SELPLG) involved in immune and inflammatory responses that lead to liver damage. Interestingly, the anti-PD drug, tolcapone, has notable therapeutic effects but also negatively affects specific genes, contributing to liver damage in patients with PD.

CONCLUSION

This study reveals the mechanisms by which PD affects liver metabolism and proposes cysteine as a biomarker and therapeutic target for liver damage in PD. Furthermore, the impact of PD treatment drugs on liver function was also evaluated. These findings provide important insights for the development of future PD treatment strategies, and further clinical research is needed to validate and optimize clinical interventions to maximize treatment efficacy and minimize side effects in patients with PD.

摘要

背景

帕金森病(PD)是一种常见的神经退行性疾病,其特征为运动迟缓、肌肉僵硬、震颤以及步态和姿势改变。临床研究已证实PD与肝脏疾病之间存在密切关联,但大多数研究集中在肝脏疾病对PD脑损伤的影响,对于理解PD患者肝脏损伤的途径和机制仍需进一步探索。

方法

本研究采用孟德尔随机化(MR)和转录组分析来探究PD相关脑损伤对肝脏健康的因果影响,确定血清代谢物(如半胱氨酸)和共同的免疫炎症途径作为中介因素。

结果

研究表明,PD相关脑损伤确实会对肝脏代谢功能产生影响。PD相关脑损伤可能会扰乱半胱氨酸的浓度,当其升高时会导致肝细胞损伤和氧化应激。此外,PD相关脑损伤可能会影响参与导致肝脏损伤的免疫和炎症反应的特定基因(如NCF1、NCF和SELPLG)。有趣的是,抗PD药物托卡朋具有显著治疗效果,但也会对特定基因产生负面影响,导致PD患者肝脏损伤。

结论

本研究揭示了PD影响肝脏代谢的机制,并提出半胱氨酸作为PD肝脏损伤的生物标志物和治疗靶点。此外,还评估了PD治疗药物对肝功能的影响。这些发现为未来PD治疗策略的制定提供了重要见解,需要进一步的临床研究来验证和优化临床干预措施,以在PD患者中最大化治疗效果并最小化副作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e927/12191201/1fe14e8933e2/JIR-18-8173-g0001.jpg

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