Epobis is a Nonerythropoietic and Neuroprotective Agonist of the Erythropoietin Receptor with Anti-Inflammatory and Memory Enhancing Effects

Abstract

The cytokine erythropoietin (EPO) stimulates proliferation and differentiation of erythroid progenitor cells. Moreover, EPO has neuroprotective, anti-inflammatory, and antioxidative effects, but the use of EPO as a neuroprotective agent is hampered by its erythropoietic activity. We have recently designed the synthetic, dendrimeric peptide, Epobis, derived from the sequence of human EPO. This peptide binds the EPO receptor and promotes neuritogenesis and neuronal cell survival. Here we demonstrate that Epobis in vitro promotes neuritogenesis in primary motoneurons and has anti-inflammatory effects as demonstrated by its ability to decrease TNF release from activated AMJ2-C8 macrophages and rat primary microglia. When administered systemically Epobis is detectable in both plasma and cerebrospinal fluid, demonstrating that the peptide crosses the blood-brain barrier. Importantly, Epobis is not erythropoietic, but systemic administration of Epobis in rats delays the clinical signs of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, and the peptide has long-term, but not short-term, effects on working memory, detected as an improved social memory 3 days after administration. These data reveal Epobis to be a nonerythropoietic and neuroprotective EPO receptor agonist with anti-inflammatory and memory enhancing properties.

Potential Effects of Angiogenesis-related Factors on the Severity of APAC and Surgical Outcomes of Trabeculectomy

“…There are emerging evidences for the neuroprotection effect of EPO both in vivo and in vitro [21,38,39]. The positive roles that EPO may play in APAC under higher dose, such as anti-apoptotic [12,13], anti-oxidant [14], and antiin ammatory [15,16] make it an ideal treatment in APAC. However, its role in angiogenesis, causing neovascularization is a dreaded occurrence in the eye [40].…”

“…However, there has been no research describing the changes of EPO and PDGF levels in APAC eyes. Recent studies have shown that both EPO and PDGF have neuroprotective functions such as anti-apoptotic [12,13], anti-oxidant [14] and anti-in ammatory properties [15,16]. Thus, the uctuations of their levels in aqueous humor may correlate with prognosis of trabeculectomy in APAC eyes.…”

Effects of erythropoietin on bacterial translocation in a rat model of experimental colitis

“…Several protective effects of EPO against ischemia were demonstrated in cell cultures and animal models, including anti-apoptotic, antioxidant, and neuroprotective effects (20,21). There are studies indicating that EPO decreases the damage caused by ischemia/reperfusion in kidneys (22) and colon (23).…”

Pathogenic substantiation of application of erythropoietin modified forms and peptide analogues as cytotprotectors

“…При системном введении Epobis крысам на модели аутоиммунного энцефалита пептид задерживает наступление признаков поражения. Также отмечен долговременный эффект пептида на рабочую и социальную память крыс [63].…”