Department of Medical Biotechnology, YeungNam University, 280 Daehak-ro, Gyeongsan, Gyeongbuk, 38541, Republic of Korea.
Int J Biol Macromol. 2018 Apr 1;109:483-491. doi: 10.1016/j.ijbiomac.2017.12.100. Epub 2017 Dec 20.
Nature has selected osmolytes to protect intracellular macromolecules exposed to denaturing conditions and stabilize proteins. Osmolytes are small naturally occurring compounds that act as chemical chaperones under changing environmental conditions and in disease states, and are present in microorganisms, animals, and plants. In the intracellular environment osmolytes naturally accumulate at high concentrations when cells/tissues are exposed to stressful conditions, which is important because protein aggregation, misfolding, and destabilization underlie the pathogenesis of several life-threatening neurodegenerative disorders. The chaperone abilities of osmolytes suggests they may be therapeutically used for the treatment of several diseases associated with protein misfolding, and their abilities to protect proteins against denaturing stresses impinges on the fundamental problem of protein stabilization, which plagues the pharmaceutical industry, biotechnologists, and researchers. We hope that this review will encourage further research in this area and catalyze increased collaboration at the interface of chemistry and biology to decipher the mechanisms and roles of protein folding, misfolding and aggregation in the fields of health and disease.
自然选择渗透物来保护暴露于变性条件下的细胞内大分子并稳定蛋白质。渗透物是在不断变化的环境条件和疾病状态下作为化学伴侣发挥作用的小的天然存在的化合物，存在于微生物、动物和植物中。在细胞内环境中，当细胞/组织暴露于应激条件下时，渗透物会自然地在高浓度下积累，这很重要，因为蛋白质聚集、错误折叠和失稳是几种危及生命的神经退行性疾病发病机制的基础。渗透物的伴侣能力表明，它们可能被用于治疗与蛋白质错误折叠相关的几种疾病，并且它们保护蛋白质免受变性应激的能力影响了困扰制药行业、生物技术家和研究人员的蛋白质稳定的基本问题。我们希望这篇综述将鼓励该领域的进一步研究，并促进化学和生物学界面的合作增加，以阐明健康和疾病领域中蛋白质折叠、错误折叠和聚集的机制和作用。
