Department of Biotechnology, Manipur University, Manipur 795003, India.
Department of Medical Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Korea.
Biomolecules. 2020 Feb 12;10(2):286. doi: 10.3390/biom10020286.
Most of the human diseases related to various proteopathies are confined to the brain, which leads to the development of various forms of neurological disorders. The human brain consists of several osmolytic compounds, such as N-Acetylaspartate (NAA), myo-inositol (mI), glutamate (Glu), glutamine (Gln), creatine (Cr), and choline-containing compounds (Cho). Among these osmolytes, the level of NAA drastically decreases under neurological conditions, and, hence, NAA is considered to be one of the most widely accepted neuronal biomarkers in several human brain disorders. To date, no data are available regarding the effect of NAA on protein stability, and, therefore, the possible effect of NAA under proteopathic conditions has not been fully uncovered. To gain an insight into the effect of NAA on protein stability, thermal denaturation and structural measurements were carried out using two model proteins at different pH values. The results indicate that NAA increases the protein stability with an enhancement of structure formation. We also observed that the stabilizing ability of NAA decreases in a pH-dependent manner. Our study indicates that NAA is an efficient protein stabilizer at a physiological pH.
大多数与各种蛋白病相关的人类疾病都局限于大脑，这导致了各种形式的神经紊乱的发展。人类大脑由几种渗透调节化合物组成，如 N-乙酰天冬氨酸（NAA）、肌醇（mI）、谷氨酸（Glu）、谷氨酰胺（Gln）、肌酸（Cr）和含胆碱化合物（Cho）。在这些渗透调节剂中，NAA 的水平在神经条件下急剧下降，因此，NAA 被认为是几种人类大脑疾病中最广泛接受的神经元生物标志物之一。迄今为止，尚无关于 NAA 对蛋白质稳定性影响的数据，因此，在蛋白病条件下 NAA 的可能影响尚未完全揭示。为了深入了解 NAA 对蛋白质稳定性的影响，我们在不同 pH 值下使用两种模型蛋白进行了热变性和结构测量。结果表明，NAA 增加了蛋白质的稳定性，促进了结构的形成。我们还观察到，NAA 的稳定能力呈 pH 依赖性降低。我们的研究表明，NAA 在生理 pH 值下是一种有效的蛋白质稳定剂。
