Erythropoietin: New Directions for the Nervous System

Abstract

New treatment strategies with erythropoietin (EPO) offer exciting opportunities to prevent the onset and progression of neurodegenerative disorders that currently lack effective therapy and can progress to devastating disability in patients. EPO and its receptor are present in multiple systems of the body and can impact disease progression in the nervous, vascular, and immune systems that ultimately affect disorders such as Alzheimer’s disease, Parkinson’s disease, retinal injury, stroke, and demyelinating disease. EPO relies upon wingless signaling with Wnt1 and an intimate relationship with the pathways of phosphoinositide 3-kinase (PI 3-K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR). Modulation of these pathways by EPO can govern the apoptotic cascade to control β-catenin, glycogen synthase kinase-3β, mitochondrial permeability, cytochrome c release, and caspase activation. Yet, EPO and each of these downstream pathways require precise biological modulation to avert complications associated with the vascular system, tumorigenesis, and progression of nervous system disorders. Further understanding of the intimate and complex relationship of EPO and the signaling pathways of Wnt, PI 3-K, Akt, and mTOR are critical for the effective clinical translation of these cell pathways into robust treatments for neurodegenerative disorders.

The Akt/mTOR/p70S6K Pathway Is Involved in the Neuroprotective Effect of Erythropoietin on Hypoxic/Ischemic Brain Injury in a Neonatal Rat Model

“…EPO signaling is likely to involve the development of neurons and glia through novel mTOR intracellular pathways after binding to the EPO receptor. Following mTOR activation, p70S6K phosphorylation is essential downstream in oligodendrocyte proliferation and myelination [20]. In the present study, mTOR along with Akt was involved in the activation of its downstream signaling pathway such as p70S6K (p70 ribosomal S6 kinase) following EPO treatment after H/I brain injury.…”

The effect of erythropoietin on bone

“…Non-hematopoietic intracellular signaling pathways include nitric oxide production and signaling via JAK2, STAT3/5, PI3K/Akt as well as MAPK pathways (Brines and Cerami 2008;Burger et al 2009;Maiese et al 2012). As reviewed by Brines, while some pleiotropic functions have been assigned to specific pathways, the activation of multiple of these intracellular signaling pathways is often required for the full pleiotropic effect (Brines and Cerami 2008).…”

“…The role of these pathways and their contribution to the net-pleiotropic effect needs further elucidation. Of particular interest are JAK2, PI3K, and mTOR signaling (Kim et al 2012;Maiese et al 2012).…”

Functional and Structural Effects of Erythropoietin Subconjunctival Administration in Glaucomatous Animals

“…Additionally to its hematopoietic effect, this cytokine has demonstrated neuroprotective and neuroregenerative properties in the central nervous system [7][8][9][10]. Many preclinical studies have been conducted in several ocular diseases such as diabetic retinopathy, retinal detachment, glaucoma, retinopathy of prematurity, age-related macular degeneration, and optic neuritis [11].…”