Studies on apoptosis regulators substances of microbial origin aiming at neuroprotection

中枢性疾病，如脑缺血疾病、阿尔茨海默病和帕金森病的神经细胞死亡，除急性应激外，通过长期应激而促进的神经细胞凋亡被认为是症状发展的原因。如果神经细胞衰老，内质网中蛋白质的折叠将变得异常，结果是旧的垃圾蛋白质将积累起来。最新的研究清楚地表明，这是神经细胞长期应激的主要原因。β-淀粉样多肽具有神经毒性作用，特别是在阿尔茨海默病方面。这种多肽的产生源于内质网应激引起的淀粉样前体蛋白(APP)的错误折叠。因此，随着进行蛋白质折叠的分子伴侣的发现，尤其是GRP78因子的发现，有望使这些中枢性疾病康复。因此，通过…的推广是意料之中的更多的发现了执行蛋白质折叠的分子伴侣，特别是这些中枢疾病可以恢复的称为GRP78的因子。通过对GRP78表达调控因子的筛选，发现了一种新的抑制微生物次级代谢产物分子伴侣表达的物质，命名为versipelostatin。尽管作为目前的抗肿瘤药物的进一步发展，这种物质可能表明作为一种中枢疾病治疗药物的相反作用，但通过检查对神经细胞的影响，很明显，与阿尔茨海默病模型相同的神经细胞死亡是被引导的，而且很明显，这种物质是证明阿尔茨海默病的发病和内质网应激关系的有用工具。应激的原因除上述内质网应激外，还与长时间的氧自由基有关。典型的情况是黑质细胞死亡，这是帕金森氏病的病理学观点。然后，通过对保护PC12细胞免受L-多巴毒性的物质的筛选及其促进，发现了新的物质氟沙宗。虽然这种物质具有低浓度的细胞保护活性和抗氧化活性，但其他抗氧化剂如维生素E不能改善L-多巴的毒性。为了揭示氟沙宗对L-多巴毒性的作用机制，用电子自旋共振方法检测了抗氧化剂的作用效果。只有氟沙宗专门清除了邻苯二酚氧化产生的自由基。关于这本书物质的更详细的机制将被研究。较少

The apoptosis to which the nerve cell death in central diseases, such as brain ischemia disease, Alzheimer's disease, and Parkinson's disease, advances by prolonged stress exposure except for an acute term is considered to be the cause of development of symptoms. If a nerve cells become senile, folding of the protein in an endoplasmic reticulum will become unusual, and, as a result, old junk proteins will be accumulated. It has been shown clearly by the latest research that this is the main causes of the long-term stress of a nerve cell. β-Amyloid peptide acts as nerve toxicity especially about Alzheimer's disease. The production of this peptide originates in misfolding of the amyloid precursor protein (APP) being caused by endoplasmic reticulum stress. Therefore, it is expected by the promotion of discovery of the molecular chaperone which performs a protein folding, especially the factor called GRP78 that these central disease can recover. Therefore, it is expected by the promotion o … More f discovery of the molecular chaperone which performs a proteinic folding, especially the factor called GRP78 that these central disease can recover. As a result of screening for the regulators of GRP78 expression, the new substance designated as versipelostatin was discovered as an inhibitor of molecular chaperone expression from the microbial secondary metabolites. Although development was furthered as a present anti-neoplasm agent in order that this substance might indicate a reverse action to be a central disease curative medicine, as a result of examining the effect over a nerve cell, it became clear that the same nerve cell death as the model of Alzheimer's disease was guided, and it became clear that this substance is a useful tool proving the onset of Alzheimer's disease and the relation of endoplasmic reticulum stress. The cause of stress is indued by the oxygen radical besides the above-mentioned endoplasmic reticulum stress over a long period of time. The typical thing is observed by the cell death of the substantia nigra which is the pathology view of Parkinson's disease. Then, as a result of screening for the substance which protects PC12 cell from the L-DOPA toxicity in which Parkinson's disease carries out and its promotion, the new substance halxazone was discovered. Although this substance showed cell protective activity by low concentration with an anti-oxidative activities, L-DOPA toxicity was not ameliorated by other antioxidants such as vitamin E. To reveal the action mechanism of halxazone against L-DOPA toxicity, the effects of antioxidants were examined using ESR. Only halxazone specifically scavenged the radical production from catechol oxidation.The still more detailed mechanism about the present book substance is due to be examined. Less