Using the synthesized peptide HAYED (5) to protect the brain against iron catalyzed radical attack in a naturally senescence Kunming mouse model

• Published in: Free radical biology & medicine 2019-01, Vol.130, p.458-470
• Main Authors: Zou, Zhenyou, Cai, Jing, Zhong, Aiguo, Zhou, Yong, Wang, Zengxian, Wu, Zhongmin, Yang, Yue, Li, Xin, Cheng, Xiaoying, Tan, Jie, Fan, Yihao, Zhang, Xiaotong, Lu, Yuxiang, Zhou, Yaping, Yang, Liu, Zhang, Chengliang, Zhao, Qiang, Fu, Derong, Shen, Qiqiong, Chen, Jie, Bai, Shi, Wu, Lijuan, Chen, Yongfeng, Chen, Xin, Chen, Jiaren, Zheng, Hongjie, Wang, Hongdian, Lou, Yingjie, Ding, Yarong, Shen, Shiyi, Ye, Ying, Chen, Lifen, Lin, Yukai, Huang, Jue, Zou, Kechun, Zhang, Jianxing, Bian, Baohua, Huang, Chengbo, Rong, Cuiping, Dai, Limiao, Xu, Yali, Cheng, Lin, Chen, Ye, Luo, Yewen, Zhang, Shanshan, Li, Liangxian
• Format: Article
• Language: English
• Subjects: Aging - drug effects; Aging - genetics; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid β peptide; Animals; Brain - drug effects; Brain - metabolism; Brain - pathology; Disease Models, Animal; Free iron ions; Gene Expression Regulation - drug effects; HAYED peptide; Humans; Iron - metabolism; Maze Learning - drug effects; Mice; Neurodegenerative Diseases - drug therapy; Neurodegenerative Diseases - pathology; Neurons - metabolism; Neurons - pathology; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; Peptide Fragments - chemical synthesis; Peptide Fragments - pharmacology; Radicals; Senescence
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2018.11.014

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. The senescence brain is characterized by high levels of iron ions, which catalyze radicals that damage the brain and bring about brain atrophy. The synthesized HAYED (5) peptide is iron-affinitive. When it enters the CSF of the senescence brain, it chelates the excessive iron, thus decreases radical catalysis and results in neurons protection and the prevention of nescence progress. [Display omitted] •Synthesized HAYED (5) peptide is effective in iron binding and radical clearance.•The peptide protected cells and the brains of senescence KM mice against radical damages.•HAYED (5) ameliorated brain blood oxygen and cognition status for senescence mice.•HAYED (5) reversed senescence-incurred inflammation without perceptible negative effect.