Erythropoietin delays disease onset in an amyotrophic lateral sclerosis model

https://doi.org/10.1016/j.expneurol.2006.11.002Get rights and content

Abstract

Erythropoietin (Epo) has been shown in the recent years to have neuroprotective activity in a variety of settings. In this study, we investigated its impact on the progression of paralysis in a mouse model simulating the human disorder amyotrophic lateral sclerosis (ALS). We found that Epo can delay the onset of motor deterioration in transgenic SOD G93A mice without prolonging their survival. Notably this effect was selective for the females only. These initial findings encourage further investigation of this biological avenue in the search for improved remedies for this fatal disease.

References (20)

  • M.T. Carri et al.

    Neurodegeneration in amyotrophic lateral sclerosis: the role of oxidative stress and altered homeostasis of metals

    Brain Res. Bull.

    (2003)
  • J.H. Veldink et al.

    Sexual differences in onset of disease and response to exercise in a transgenic model of ALS

    Neuromuscul. Disord.

    (2003)
  • M. Brines et al.

    Emerging biological roles for erythropoietin in the nervous system

    Nat. Rev., Neurosci.

    (2005)
  • M.L. Brines et al.

    Erythropoietin crosses the blood–brain barrier to protect against experimental brain injury

    Proc. Natl. Acad. Sci. U. S. A.

    (2000)
  • L.I. Bruijn et al.

    Unraveling the mechanisms involved in motor neuron degeneration in ALS

    Annu. Rev. Neurosci.

    (2004)
  • M. Celik et al.

    Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury

    Proc. Natl. Acad. Sci. U. S. A.

    (2002)
  • M.A. del Aguila et al.

    Prognosis in amyotrophic lateral sclerosis: a population-based study

    Neurology

    (2003)
  • H. Ehrenreich et al.

    Erythropoietin therapy for acute stroke is both safe and beneficial

    Mol. Med.

    (2002)
  • S. Erbayraktar et al.

    Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo

    Proc. Natl. Acad. Sci. U. S. A.

    (2003)
  • M. Farooque et al.

    Gender-related differences in recovery of locomotor function after spinal cord injury in mice

    Spinal Cord

    (2006)
There are more references available in the full text version of this article.

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