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J. Clin. Med. 2018, 7(2), 24; https://doi.org/10.3390/jcm7020024

Alternative Erythropoietin Receptors in the Nervous System

1
Department of Biology, Truman State University, Kirksville, MO 63501, USA
2
Department of Cellular Neurobiology, Institute for Zoology, Georg-August-University Göttingen, 37073 Göttingen, Germany
*
Authors to whom correspondence should be addressed.
Received: 2 January 2018 / Revised: 24 January 2018 / Accepted: 26 January 2018 / Published: 2 February 2018
(This article belongs to the Special Issue Injury and Repair in the Nervous System)
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Abstract

In addition to its regulatory function in the formation of red blood cells (erythropoiesis) in vertebrates, Erythropoietin (Epo) contributes to beneficial functions in a variety of non-hematopoietic tissues including the nervous system. Epo protects cells from apoptosis, reduces inflammatory responses and supports re-establishment of compromised functions by stimulating proliferation, migration and differentiation to compensate for lost or injured cells. Similar neuroprotective and regenerative functions of Epo have been described in the nervous systems of both vertebrates and invertebrates, indicating that tissue-protective Epo-like signaling has evolved prior to its erythropoietic function in the vertebrate lineage. Epo mediates its erythropoietic function through a homodimeric Epo receptor (EpoR) that is also widely expressed in the nervous system. However, identification of neuroprotective but non-erythropoietic Epo splice variants and Epo derivatives indicated the existence of other types of Epo receptors. In this review, we summarize evidence for potential Epo receptors that might mediate Epo’s tissue-protective function in non-hematopoietic tissue, with focus on the nervous system. In particular, besides EpoR, we discuss three other potential neuroprotective Epo receptors: (1) a heteroreceptor consisting of EpoR and common beta receptor (βcR), (2) the Ephrin (Eph) B4 receptor and (3) the human orphan cytokine receptor-like factor 3 (CRLF3). View Full-Text
Keywords: erythropoietin; non-hematopoietic functions; neuroprotection; regeneration; alternative erythropoietin receptors; common β chain receptor; ephrin B4 receptor; cytokine receptor-like factor 3 erythropoietin; non-hematopoietic functions; neuroprotection; regeneration; alternative erythropoietin receptors; common β chain receptor; ephrin B4 receptor; cytokine receptor-like factor 3
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Ostrowski, D.; Heinrich, R. Alternative Erythropoietin Receptors in the Nervous System. J. Clin. Med. 2018, 7, 24.

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