Chiang Ping-I, Chang Kuo-Hsuan, Tang Hsiang-Yu, Wu Yih-Ru, Cheng Mei-Ling, Chen Chiung-Mei
Department of Medical Education, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231, Taiwan.
Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Metabolites. 2024 Jul 20;14(7):394. doi: 10.3390/metabo14070394.
Huntington's disease (HD) is characterized by progressive involuntary chorea movements and cognitive decline. Recent research indicates that metabolic disturbance may play a role in its pathogenesis. Bile acids, produced during cholesterol metabolism in the liver, have been linked to neurodegenerative conditions. This study investigated variations in plasma bile acid profiles among individuals with HD. Plasma levels of 16 primary and secondary bile acids and their conjugates were analyzed in 20 healthy controls and 33 HD patients, including 24 with symptoms (symHD) and 9 carriers in the presymptomatic stage (preHD). HD patients exhibited significantly higher levels of glycochenodeoxycholic acid (GCDCA) and glycoursodeoxycholic acid (GUDCA) compared to healthy controls. Conversely, isolithocholic acid levels were notably lower in the HD group. Neurotoxic bile acids (glycocholic acid (GCA) + glycodeoxycholic acid (GDCA) + GCDCA) were elevated in symHD patients, while levels of neuroprotective bile acids (ursodeoxycholic acid (UDCA) + GUDCA + tauroursodeoxycholic acid (TUDCA)) were higher in preHD carriers, indicating a compensatory response to early neuronal damage. These results underscore the importance of changes in plasma bile acid profiles in HD and their potential involvement in disease mechanisms. The identified bile acids (GCDCA, GUDCA, and isolithocholic acid) could potentially serve as markers to distinguish between HD stages and healthy individuals. Nonetheless, further research is warranted to fully understand the clinical implications of these findings and their potential as diagnostic or therapeutic tools for HD.
亨廷顿舞蹈症（HD）的特征是进行性非自主性舞蹈样运动和认知能力下降。最近的研究表明，代谢紊乱可能在其发病机制中起作用。肝脏中胆固醇代谢过程产生的胆汁酸与神经退行性疾病有关。本研究调查了HD患者血浆胆汁酸谱的变化。分析了20名健康对照者和33名HD患者（包括24名有症状者（symHD）和9名症状前阶段携带者（preHD））血浆中16种初级和次级胆汁酸及其共轭物的水平。与健康对照者相比，HD患者的甘氨鹅去氧胆酸（GCDCA）和甘氨熊去氧胆酸（GUDCA）水平显著更高。相反，HD组中异石胆酸水平明显更低。神经毒性胆汁酸（甘胆酸（GCA）+甘氨脱氧胆酸（GDCA）+GCDCA）在symHD患者中升高，而神经保护性胆汁酸（熊去氧胆酸（UDCA）+GUDCA+牛磺熊去氧胆酸（TUDCA））在preHD携带者中更高，表明对早期神经元损伤的代偿反应。这些结果强调了HD患者血浆胆汁酸谱变化的重要性及其在疾病机制中的潜在作用。所鉴定的胆汁酸（GCDCA、GUDCA和异石胆酸）可能作为区分HD阶段和健康个体的标志物。尽管如此，仍需要进一步研究以充分了解这些发现的临床意义及其作为HD诊断或治疗工具的潜力。
