An Overview of Neuroprotective Effects of Erythropoietin Against Neurological Disorders: Beyond Erythropoiesis

J Biochem Mol Toxicol. 2025 Sep;39(9):e70442. doi: 10.1002/jbt.70442.

ABSTRACT

Brain related disorders are a set of medical ailments that cause motor incoordination, cognitive and memory problems due to neurodegeneration in the brain. Although current therapies alleviate symptoms, they fail to target the fundamental pathological processes driving the disorders. A hematopoietic growth factor, Erythropoietin, stimulates erythroid cell formation and is therapeutically applied for the treatment of anemia. Furthermore, Erythropoietin has shown improved neurological outcomes in preclinical models and is being investigated as a potential therapeutic agent for neurodegenerative disorders. Erythropoietin is potential target for the regulation of numerous cellular signal pathways to enhance the neuronal survival, promote neuronal differentiation via binding of Erythropoietin-to-Erythropoietin receptor to stimulate the protein Janus-tyrosine kinase 2 followed by regulation of protein kinase B, signal transducer and stimulators of transcription 5, protein tyrosine phosphatases, mitogen-activated protein kinases, nuclear factor kB and Wnt1. Numerous research studies have evaluated the therapeutic potential of Erythropoietin against several neurological disorders including Alzheimer's disease, Parkinson's disease, neuroinflammation and epilepsy and highlight that Erythropoietin exhibits significant neuroprotective effects by counteracting apoptosis, neuroinflammatory process, reactive oxygen species overburden and neuronal death, consequently, prevent the progression of such diseases. However, two major challenges in developing erythropoietin as a neuroprotective agent include optimizing its therapeutic window and addressing safety concerns, particularly its adverse interaction with tissue plasminogen activator, which has been shown to increase the risk of hemorrhagic complications in ischemic stroke patients. In present review, we discuss the neurotherapeutic applications of Erythropoietin against brain related disorders beyond erythropoiesis. In conclusion, it can be assumed that Erythropoietin could be an alternative therapeutic option for the management of neurological disorders.

PMID:40808348 | DOI:10.1002/jbt.70442