Yap Kah Hui, Azmin Shahrul, Makpol Suzana, Damanhuri Hanafi Ahmad, Mustapha Muzaimi, Hamzah Jemaima Che, Ibrahim Norlinah Mohamed
Department of Medicine, UKM Medical Centre, Kuala Lumpur, Malaysia.
Department of Biochemistry, UKM Medical Centre, Kuala Lumpur, Malaysia.
Neural Regen Res. 2023 Jun;18(6):1179-1185. doi: 10.4103/1673-5374.360164.
Trehalose, a unique nonreducing crystalline disaccharide, is a potential disease-modifying treatment for neurodegenerative diseases associated with protein misfolding and aggregation due to aging, intrinsic mutations, or autophagy dysregulation. This systematic review summarizes the effects of trehalose on its underlying mechanisms in animal models of selected neurodegenerative disorders (tau pathology, synucleinopathy, polyglutamine tract, and motor neuron diseases). All animal studies on neurodegenerative diseases treated with trehalose published in Medline (accessed via EBSCOhost) and Scopus were considered. Of the 2259 studies screened, 29 met the eligibility criteria. According to the SYstematic Review Center for Laboratory Animal Experiment (SYRCLE) risk of bias tool, we reported 22 out of 29 studies with a high risk of bias. The present findings support the purported role of trehalose in autophagic flux and protein refolding. This review identified several other lesser-known pathways, including modifying amyloid precursor protein processing, inhibition of reactive gliosis, the integrity of the blood-brain barrier, activation of growth factors, upregulation of the downstream antioxidant signaling pathway, and protection against mitochondrial defects. The absence of adverse events and improvements in the outcome parameters were observed in some studies, which supports the transition to human clinical trials. It is possible to conclude that trehalose exerts its neuroprotective effects through both direct and indirect pathways. However, heterogeneous methodologies and outcome measures across the studies rendered it impossible to derive a definitive conclusion. Translational studies on trehalose would need to clarify three important questions: 1) bioavailability with oral administration, 2) optimal time window to confer neuroprotective benefits, and 3) optimal dosage to confer neuroprotection.
海藻糖是一种独特的非还原性结晶二糖，对于因衰老、内在突变或自噬失调导致蛋白质错误折叠和聚集的神经退行性疾病，它是一种有潜力的改善疾病的治疗方法。本系统评价总结了海藻糖对所选神经退行性疾病（tau病理、突触核蛋白病、多聚谷氨酰胺 tract和运动神经元疾病）动物模型的潜在机制的影响。我们检索了通过EBSCOhost访问的Medline和Scopus数据库中所有关于用海藻糖治疗神经退行性疾病的动物研究。在筛选的2259项研究中，29项符合纳入标准。根据实验室动物实验系统评价中心（SYRCLE）的偏倚风险工具，我们报告29项研究中有22项存在高偏倚风险。目前的研究结果支持海藻糖在自噬通量和蛋白质重折叠中所声称的作用。本综述还确定了其他几个鲜为人知的途径，包括修饰淀粉样前体蛋白加工、抑制反应性胶质增生、血脑屏障的完整性、生长因子的激活、下游抗氧化信号通路的上调以及对线粒体缺陷的保护。一些研究中未观察到不良事件，且结果参数有所改善，这支持向人体临床试验的过渡。可以得出结论，海藻糖通过直接和间接途径发挥其神经保护作用。然而，各研究中方法和结果测量的异质性使得无法得出明确结论。关于海藻糖的转化研究需要阐明三个重要问题：1）口服给药的生物利用度，2）赋予神经保护益处的最佳时间窗，以及3）赋予神经保护作用的最佳剂量。
