Department of Anatomy, Konkuk University, Seoul, 05029, Korea.
Research Institute of Medical Science, Konkuk University, Seoul, 05029, Korea.
Cell Death Dis. 2018 Jun 15;9(7):712. doi: 10.1038/s41419-018-0749-9.
Trehalose is a non-reducing disaccharide with two glucose molecules linked through an α, α-1,1-glucosidic bond. Trehalose has received attention for the past few decades for its role in neuroprotection especially in animal models of various neurodegenerative diseases, such as Parkinson and Huntington diseases. The mechanism underlying the neuroprotective effects of trehalose remains elusive. The prevailing hypothesis is that trehalose protects neurons by inducing autophagy, thereby clearing protein aggregates. Some of the animal studies showed activation of autophagy and reduced protein aggregates after trehalose administration in neurodegenerative disease models, seemingly supporting the autophagy induction hypothesis. However, results from cell studies have been less certain; although many studies claim that trehalose induces autophagy and reduces protein aggregates, the studies have their weaknesses, failing to provide sufficient evidence for the autophagy induction theory. Furthermore, a recent study with a thorough examination of autophagy flux showed that trehalose interfered with the flux from autophagosome to autolysosome, raising controversy on the direct effects of trehalose on autophagy. This review summarizes the fundamental properties of trehalose and the studies on its effects on neurodegenerative diseases. We also discuss the controversy related to the autophagy induction theory and seek to explain how trehalose works in neuroprotection.
海藻糖是一种由两个葡萄糖分子通过α,α-1,1-糖苷键连接而成的非还原二糖。在过去的几十年中，海藻糖因其在神经保护中的作用而受到关注，特别是在各种神经退行性疾病的动物模型中，如帕金森病和亨廷顿病。海藻糖发挥神经保护作用的机制仍不清楚。目前流行的假说认为，海藻糖通过诱导自噬来保护神经元，从而清除蛋白质聚集体。一些动物研究表明，在神经退行性疾病模型中，海藻糖给药后会激活自噬并减少蛋白质聚集体，这似乎支持自噬诱导假说。然而，细胞研究的结果却不太确定；尽管许多研究声称海藻糖诱导自噬并减少蛋白质聚集体，但这些研究存在缺陷，未能为自噬诱导理论提供充分的证据。此外，最近一项对自噬流进行了深入检查的研究表明，海藻糖干扰了自噬小体到自溶酶体的流，这引发了人们对海藻糖对自噬的直接影响的争议。本综述总结了海藻糖的基本特性及其在神经退行性疾病中的作用的研究。我们还讨论了与自噬诱导理论相关的争议，并试图解释海藻糖在神经保护中的作用机制。
