Erythropoietin and its Analogues as Therapeutics for Neurological Diseases

Erythropoietin (EPO), originally discovered as a cytokine that primarily acts on the erythroid progenitor cells in the bone marrow, has recently been recognized to play a crucial role in the nervous system. In response to damage and inflammation, locally-produced EPO is released by astrocytes, microglia, neurons, pericytes, and endothelial cells, which in turn activates widespread EPO receptor expression by multiple nervous system cells. This results in attenuated neuronal apoptotic and death processes and the stimulation of stem cell differentiation and repair. These activities have also been examined in contexts where EPO release was modulated by external stimuli, e.g., hypoxia, inflammation and iron handling alterations. A key step in this pathway is represented by the qualitative and quantitative distribution of different isoforms of the EPO receptors in the target cells at specific developmental stages. The existence of receptor isoforms has allowed for the development of non-erythropoietic analogues which are fully neuroprotective while not stimulating red cell production or thrombosis. These are being evaluated for clinical use as therapy.

The aim of this research topic is to foster an interdisciplinary exchange of the advances in knowledge concerning erythropoietin (EPO), its derivates, receptor isoforms and target cells in the nervous system. We expect that investigating the mechanisms by which EPO and its analogues affect the nervous system, we would be able to further refine therapeutic strategies aimed at treating neurological diseases. Continued multidisciplinary research in this area at several levels, from chemistry to neuropathology, will lead to a more comprehensive understanding of neurobiology in health, as well as of the nervous system responses to injury and neuropathological processes.

We expect to receive both Original Research and Reviews articles aimed at assessing the potential role of EPO and its analogues in driving neuroprotection in acute injury and neurodegenerative diseases. We anticipate that contributions based essentially on basic or clinical data will not be considered positively in the favor of multidisciplinary efforts in the logic “from bench to bed – and return”.
We welcome submissions covering the following topics:

• Summarizing the roles of endogenous EPO in normal neurobiology, development, and neuropathology;
• Dissecting the biological activities and molecular mechanisms underlying the EPO neuroprotective effects;
• Dissecting EPO effect on cell metabolism as therapeutic target;
• Identifying EPO analogues that may act as potential therapeutical targets;
• Assigning roles for specific cell-type EPO receptor isoforms;
• Elucidating which acute pathologies (e.g., spinal cord injury, perinatal brain injury) or chronic neurodegenerative diseases (e.g., Parkinson disease, amyotrophic lateral sclerosis, Huntington disease, and psychiatric conditions) may be targetable for EPO-based therapies;
• Determining effects of EPO/analogues on cognitive function/depression/schizophrenia;
• Identifying external stimuli, e.g., hypoxia, hyperoxia, brain hypoxia and ischemia, inflammation, iron dysfunction, oxidative stress etc., with potential positive or negative interference with EPO-based mechanisms;
• Introducing novel multidisciplinary experimental models aimed at covering the gap between basic mechanisms and clinical outcomes;
• Assessing potential clinical advances (e.g., trials in neuropathy).



Topic Editor Michael Brines is employed by Araim Pharmaceuticals. The other Topic Editors declare no competing interests with regard to the Research Topic subject.