A novel endogenous erythropoietin mediated pathway prevents axonal degeneration

Sanjay C. Keswani, Ulas Buldanlioglu, Angela Fischer, Nicole Reed, Michelle Polley, Hong Liang, Chunhua Zhou, Christelene Jack, Gerhard J. Leitz, Ahmet Hoke

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

Clinically relevant peripheral neuropathies (such as diabetic and human immunodeficiency virus sensory neuropathies) are characterized by distal axonal degeneration, rather than neuronal death. Here, we describe a novel, endogenous pathway that prevents axonal degeneration. We show that in response to axonal injury, periaxonal Schwann cells release erythropoietin (EPO), which via EPO receptor binding on neurons, prevents axonal degeneration. We demonstrate that the relevant axonal injury signal that stimulates EPO production from surrounding glial cells is nitric oxide. In addition, we show that this endogenous pathway can be therapeutically exploited by administering exogenous EPO. In an animal model of distal axonopathy, systemic EPO administration prevents axonal degeneration, and this is associated with a reduction in limb weakness and neuropathic pain behavior. Our in vivo and in vitro data suggest that EPO prevents axonal degeneration and therefore may be therapeutically useful in a wide variety of human neurological diseases characterized by axonopathy.

Original languageEnglish (US)
Pages (from-to)815-826
Number of pages12
JournalAnnals of neurology
Volume56
Issue number6
DOIs
StatePublished - Dec 2004

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Fingerprint

Dive into the research topics of 'A novel endogenous erythropoietin mediated pathway prevents axonal degeneration'. Together they form a unique fingerprint.

Cite this