The bs-YHEDA peptide protects the brains of senile mice and thus recovers intelligence by reducing iron and free radicals

• Published in: Free radical biology & medicine 2022-09, Vol.190, p.216-225
• Main Authors: Gao, Xiaodie, Wang, Zhigang, Xiong, Lijun, Wu, Fengyao, Gan, Xinying, Liu, Jinlian, Huang, Xiansheng, Liu, Juxia, Tang, Liling, Li, Yanmei, Huang, Jinli, Huang, Yuping, Li, Wenyang, Zeng, Hongji, Ban, Yunfei, Chen, Tingting, He, Suyuan, Lin, Anni, Han, Fei, Guo, Xuefeng, Yu, Qiming, Shu, Wei, Zhang, Bo, Zou, Ruyi, Zhou, Yong, Chen, Yongfeng, Tian, Haibo, Wei, Wenjia, Zhang, Zhen, Wei, Chuandong, Wei, Yuhua, Liu, Huihua, Yao, Hua, Chen, Qiang, Zou, Zhenyou
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Blood–brain barrier; bs-YHEDA Peptide; Iron; Low-density lipoprotein receptor; Radicals
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2022.08.014

Iron accumulates in the brain with age and catalyzes free radical damage to neurons, thus playing a pathogenic role in Alzheimer's disease (AD). To decrease the incidence of AD, we synthesized the iron-affinitive peptide 5YHEDA to scavenge the excess iron in the senile brain. However, the blood–brain barrier (BBB) blocks the entrance of macromolecules into the brain, thus decreasing the therapeutic effects. To facilitate the entrance of the 5YHEDA peptide, we linked the low-density lipoprotein receptor (LDLR)-binding segment of ApoB-100 to 5YHEDA (named “bs-YHEDA”). The results of intravenous injections of bs-5YHEDA into senescent mice demonstrated that bs-YHEDA entered the brain, increased ferriportin levels, reduced iron and free radical levels, decreased the consequences of neuronal necrosis and ameliorated cognitive disfunction without kidney or liver damage. bs-5YHEDA is a safe iron and free radical remover that potentially alleviates aging and Alzheimer's disease. [Display omitted] •A peptide 5YHEDA was innvated to chelate free iron ions in senile brain.•By linking the LDLR binding segment to 5YHEDA, the peptide is able to cross Blood-Brain Barrier and enter into brain.•The peptide can prevent ROS generation by sequestering free iron ions thus protect neurons and ameliorated cognitive disfunction for senescent mouse.•bs-5YHEDA peptide can enhance the excretion of iron by resuming the expression of ferriportin.