Neuroprotective factor, Colibelin, against ALS related insults : Characterization by circular Dichroism and sedimentation equilibrium

肌萎缩侧索硬化症（amyotrophiclateralsclerosis，ALS）是最常见的运动神经元疾病，以运动神经元的进行性全身性丧失为特征。对于ALS没有足够有效的治疗方法。我们以前曾报道，侧脑室注射ADNF，胶质源性神经营养肽，提高运动性能的G93 A-SOD 1转基因小鼠。在这项研究中，我们发现Colivelin，ADNF的杂合肽和最有效的Humanin衍生物AGAC 8 R-BNG 17，在100 fM左右对ALS和阿尔茨海默病（AD）相关损伤发挥神经保护作用。Colivelin可延长ALS模型小鼠的存活时间，而ADNF则不能。我们进一步发现Colivelin能够抑制由侧脑室注射Abeta 25.35-或Abeta 42引起的空间工作记忆障碍。为了研究Colivelin的飞摩尔神经保护作用，我们通过环状dic对组成肽ADNF和AGAC 8 R-HNG 17以及Colivelin进行了表征。 ...更多信息 色度（CD）和沉降平衡。ADNF在其浓度范围内均为单体，提示其在生理条件下以单体形式发挥神经保护作用。沉降平衡实验也证明了Colivelinl的单体结构。CD分析表明Colivelin是一种完全不同于ADNF和AGAC 8 R-HNG 17简单混合物的分子。二级结构在水中比在PBS中更无序。肽在水中的结构几乎不依赖于肽浓度和温度。相反，PBS中的肽结构与水中的结构显著不同。在PBS中观察到的不同结构似乎是由于肽通过疏水相互作用的自缔合。野生型Humanin也表现类似，即，它在水中呈现无序结构，但在PBS中经历构象变化。少

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, characterized by progressive systemic loss of motor neurons. There is no sufficiently effective therapy for ALS. We have previously reported that intracerebroventicular injection of ADNF, a glia-derived neurotrophic peptide, improves motor performance of G93A-SOD 1 transgenic mice. In this study, we found that Colivelin, hybrid peptide of ADNF and a most potent Humanin derivative, AGAC8R-BNG17, exerts its neuroprotection against both ALS and Alzheimer's disease (AD) related insults at around 100 fM. Colivelin prolongs survival of an ALS model mice though ADNF could not. We further found that Colivelin was able to suppress impairment in spatial working memory induced by intracerebroventicular injection of Abeta 25.35-or Abeta 42.In order to investigate the femtomolar acting neuroprotection of Colivelin, we have been characterizing the component peptides ADNF and AGAC8R-HNG17 as well as Colivelin by circular dic … More hroism (CD) and sedimentation equilibrium. ADNF was a monomer in solution over the wide range of its concentration suggesting that it exerts neuroprotection with monomer form in physiological condition. The sedimentation equilibrium experiments demonstrated monomeric structure of Colivelinl as well. It was suggested by CD analysis that Colivelin was a completely different molecule from simple mixture molecules of ADNF and AGAC8R-HNG17.The structure of a highly potent HNG was examined by CD. The secondary structure is more disordered in water than in PBS. The peptide structure in water is little dependent on both peptide concentration and temperature. On the contrary, the peptide structure was significantly different in PBS from the structure in water. The observed different structure in PBS appears to be due to self-association of the peptide via hydrophobic interaction. The wild-type Humanin also behaved similarly, i.e., it assumed a disordered structure in water but underwent conformational changes in PBS. Less