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

肌萎缩侧索硬化症(ALS)是最常见的运动神经元疾病，以进行性运动神经元的全身性丢失为特征。目前还没有足够有效的治疗ALS的方法。我们之前已经报道，脑室注射ADNF，一种神经胶质细胞衍生的神经营养肽，可以改善G93A-SOD1转基因小鼠的运动能力。在这项研究中，我们发现，Colivelin，ADNF的杂交肽和最有效的人蛋白衍生物AGAC8R-BNG17，在大约100 fM的频率下对ALS和阿尔茨海默病(AD)相关的侮辱发挥神经保护作用。Colivelin可以延长ALS模型小鼠的存活时间，但ADNF不能。我们进一步发现，Colivelin能够抑制脑室注射Abeta25.35-或Abeta42所致的空间工作记忆障碍。为了研究Colivelin的股骨分子作用神经保护作用，我们一直在用环状…研究Colivelin的组成多肽ADNf和AGAC8R-HNG17以及Colivelin更多的有色(Cd)和沉积平衡。ADNF在较宽的浓度范围内以单体形式存在于溶液中，在生理条件下以单体形式发挥神经保护作用。沉降平衡实验也证实了Colivelinl的单体结构。CD分析表明，Colivelin是一个与ADNF和AGAC8R-HNG17简单混合分子完全不同的分子。CD分析证实了一个高效的HNG的结构。在水中的二级结构比在PbS中更无序。水中的多肽结构几乎不受多肽浓度和温度的影响。相反，PBS中的多肽结构与水中的结构明显不同。在PBS中观察到的不同结构似乎是由于多肽通过疏水相互作用而自结合。野生型人也有类似的行为，即在水中呈现无序结构，但在PBS中发生构象变化。较少

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