Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin, GX 541199, China; Medical School of Taizhou University, Taizhou, ZJ 318000, China; Biochemistry Department, Purdue University, West Lafayette, IN 47906, USA.
Genetic Department of Nanjing Medical University, Nanjing, JS 210000, China.
Free Radic Biol Med. 2019 Jan;130:458-470. doi: 10.1016/j.freeradbiomed.2018.11.014. Epub 2018 Nov 15.
Alzheimer's disease (AD) is a progressive neurodegenerative disease of the brain. It cannot be cured currently, and those suffering from AD place a great burden on their caregivers and society. AD is characterized by high levels of iron ions in the brain, which catalyze radicals that damage the neurons. Knowing that the Aβ42 peptide precipitates iron by binding iron ions at amino acid residues D1, E3, H11, H13, and H14, we synthesized a 5-repeat (HAYED) sequence peptide. By treating iron-stressed SH-SY5Y cells with it and injecting it into the cerebrospinal fluid (CSF) of naturally senescence Kunming mouse, which displaying AD-similar symptoms such as learning and memory dysfunction, neuron degeneration and high level of iron in brain, we found that HAYED (5) decreased the iron and radical levels in the cell culture medium and in the CSF. Specially, the synthesized peptide prevented cell and brain damage. Furthermore, functional magnetic resonance imaging (fMRI), Morris water maze and passive avoidance tests demonstrated that the peptide ameliorated brain blood-oxygen metabolism and slowed cognitive loss in the experimental senescence mice, and clinical and blood tests showed that HAYED (5) was innoxious to the kidney, the liver and blood and offset the AD-associated inflammation and anemia.
阿尔茨海默病(AD)是一种大脑进行性神经退行性疾病。目前无法治愈,AD 患者给其护理人员和社会带来了巨大的负担。AD 的特征是大脑中铁离子水平升高,这些铁离子会催化自由基损伤神经元。我们知道 Aβ42 肽通过结合氨基酸残基 D1、E3、H11、H13 和 H14 上的铁离子来沉淀铁,因此我们合成了一个 5 重复(HAYED)序列肽。通过用它处理铁应激的 SH-SY5Y 细胞,并将其注入具有 AD 样症状(如学习和记忆功能障碍、神经元变性和大脑中铁水平升高)的自然衰老昆明小鼠的脑脊液(CSF)中,我们发现 HAYED(5)降低了细胞培养物和 CSF 中的铁和自由基水平。特别是,合成的肽预防了细胞和大脑损伤。此外,功能磁共振成像(fMRI)、Morris 水迷宫和被动回避测试表明,该肽改善了实验性衰老小鼠的大脑血氧代谢并减缓了认知能力下降,临床和血液测试表明 HAYED(5)对肾脏、肝脏和血液均无毒副作用,并能抵消 AD 相关的炎症和贫血。