Neuronal cell death in Alzheimer's disease and a neuroprotective factor, humanin
Neuronal cell death in Alzheimer's disease and a neuroprotective factor, humanin
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DOI：
10.2174/157015906776359577
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发表时间：
2006-04-01
影响因子：
5.3
通讯作者：
Kita, Y
中科院分区：
文献类型：
--
作者：
Niikura, T;Tajima, H;Kita, Y
由神经元缺失引起的脑萎缩是阿尔茨海默病（A β）的一个突出病理特征。β淀粉样蛋白（β D）是老年斑的主要成分，被认为在神经元细胞死亡中起核心作用。除了去除毒性A β外，直接抑制神经元损失是AD治疗的重要组成部分;然而，尚未开发出此类神经保护疗法。过量的A β引起多种细胞毒性机制，包括细胞内Ca 2+水平升高、氧化应激和受体介导的细胞死亡级联激活。由A β诱导的细胞毒性机制的这种多样性清楚地表明AD相关神经元细胞死亡的复杂性质。我们已经确定了一个24个残基的肽，Humanin（HN），抑制在体外神经元细胞死亡所造成的所有AD相关的侮辱，包括A β，到目前为止测试。HN的抗AD作用已在体内使用具有A β诱导的遗忘症的小鼠进一步证实。总之，HN在体外和体内针对AD相关细胞毒性的这种有效的神经保护活性表明HN在旨在控制神经元死亡的新型AD疗法中的潜在临床应用。
Brain atrophy caused by neuronal loss is a prominent pathological feature of Alzheimer's disease (A beta). Amyloid beta (beta D), the major component of senile plaques, is considered to play a central role in neuronal cell death. In addition to removal of the toxic A beta, direct suppression of neuronal loss is an essential part of AD treatment; however, no such neuroprotective therapies have been developed. Excess amount of A beta evokes multiple cytotoxic mechanisms, involving increase of the intracellular Ca2+ level, oxidative stress, and receptor-mediated activation of cell-death cascades. Such diversity in cytotoxic mechanisms induced by A beta clearly indicates a complex nature of the AD-related neuronal cell death. We have identified a 24-residue peptide, Humanin (HN), which suppresses in vitro neuronal cell death caused by all AD-related insults, including A beta, so far tested. The anti-AD effect of HN has been further confirmed in vivo using mice with A beta-induced amnesia. Altogether, such potent neuroprotective activity of HN against AD-relevant cytotoxicity both hi vitro and in vivo suggests the potential clinical applications of HN in novel AD therapies aimed at controlling neuronal death.