Second-generation non-hematopoietic erythropoietin-derived peptide for neuroprotection

Redox Biology

Seong-Ryong Lee¹  Seung-Jun Yoo¹  Cheil Moon²  So Yeon Kim²  Chang-Hun Lee³  Bongki Cho⁴  Yun-Il Lee⁴ 

[1] Cognitive Sciences, Graduate School, DGIST, Daegu, 42988, South Korea;Convergence Research Advanced Centre for Olfaction, DGIST, Daegu, 42988, South Korea;Division of Biotechnology, DGIST, Daegu, 42988, South Korea;;Department of Brain &

关键词: Erythropoietin;    Erythropoietin receptor;    Peptide;    Neuroprotection;    Hypoxia;    Ischemia;   

DOI  :  

来源: DOAJ

【 摘 要 】

Erythropoietin (EPO) is a well-known erythropoietic cytokine having a tissue-protective effect in various tissues against hypoxic stress, including the brain. Thus, its recombinants may function as neuroprotective compounds. However, despite considerable neuroprotective effects, the EPO-based therapeutic approach has side effects, including hyper-erythropoietic and tumorigenic effects. Therefore, some modified forms and derivatives of EPO have been proposed to minimize the side effects. In this study, we generated divergently modified new peptide analogs derived from helix C of EPO, with several amino acid replacements that interact with erythropoietin receptors (EPORs). This modification resulted in unique binding potency to EPOR. Unlike recombinant EPO, among the peptides, ML1-h3 exhibited a potent neuroprotective effect against oxidative stress without additional induction of cell-proliferation, owing to a differential activating mode of EPOR signaling. Furthermore, it inhibited neuronal death and brain injury under hypoxic stress in vitro and in an in vivo ischemic brain injury model. Therefore, the divergent modification of EPO-derivatives for affinity to EPOR could provide a basis for a more advanced and optimal neuroprotective strategy.

【 授权许可】

Unknown