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Introduction to the Series on EPO

To watch the companion video to this series, click here.


This series of four articles summarizes the value of erythropoietin, its analogues, and derivatives for the improvement of cognitive function. The first article describes natural erythropoietin and what is known about its signaling mechanisms in the human body. The second article surveys man-made erythropoietic molecules. The third article summarizes the protective effects of erythropoietin on the body and brain. The fourth article provides an up-to-date review of non-erythropoietic analogues and derivatives that have been developed for the purpose of enhancing cognitive function. Finally, the fifth article speculates on the value of EPO’s non-erythropoietic analogues and derivatives for the person interested in protecting and improving cognitive function.


Erythropoietin (EPO) regulates red blood cell production (erythropoiesis) in the body. Though its erythropoietic effect is the reason it is used by anemics and athletes, its neuroprotective and neurotrophic effect has become the focus of academic attention for the last two decades. The EPO molecule does not pass the blood-brain barrier (BBB) easily because of its size, necessitating high-dose treatments to experience cognitive benefits. At these high doses, the erythropoietic effect becomes hazardous to cardiovascular health because it gives the blood too much viscosity.

Though there are many EPO analogues that maintain its erythropoietic effect, there are also lesser-known alternatives that both readily cross the BBB and lack an erythropoietic effect. Two of these are naturally found derivatives of EPO (NeuroEPO and EPOL), two synthetic derivatives either lack sialic acid or are carbamylated (AsialoEPO and CEBO, respectively), and seven are small, mimetic peptides developed by three research teams (HBP, HBSP, pHBSP, EPOTRIS, EPOBIS, NL100, and JM-4).

These eleven molecules are attractive because of their profoundly trophic and neuroprotective qualities. CEBO is unique in being nonangiogenic, though an added benefit may be derived of a second molecule with an EPOR-mediated angiogenic effect, used intermittently.

To read the first article in the series, click here.

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