Neuroprotective effect of oxidized galectin-1 in a transgenic mouse model of amyotrophic lateral sclerosis

Ren Chang-Hong, Manabu Wada, Shingo Koyama, Hideki Kimura, Shigeki Arawaka, Toru Kawanami, Keiji Kurita, Toshihiko Kadoya, Masashi Aoki, Yasuto Itoyama, Takeo Kato

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41 Citations (Scopus)

Abstract

Abnormal accumulation of neurofilaments in motor neurons is a characteristic pathological finding in amyotrophic lateral sclerosis (ALS). Recently, we revealed that galectin-1, whose oxidized form has axonal regeneration-enhancing activity, accumulates in the neurofilamentous lesions in ALS. To investigate whether oxidized galectin-1 has a beneficial effect on ALS, oxidized recombinant human galectin-1 (rhGAL-1/ox) or physiological saline was injected into the left gastrocnemius muscle of the transgenic mice over-expressing a mutant copper/zinc superoxide dismutase (SOD1) with a substitution of histidine to arginine at position 46 (H46R SOD1). The H46R SOD1 transgenic mice, which represented a new animal model of familial ALS, were subsequently assessed for their disease onset, life span, duration of illness, and motor function. Furthermore, the number of remaining large anterior horn cells of spinal cords was also compared between the two groups. The results showed that administration of rhGAL-1/ox to the mice delayed the onset of their disease and prolonged the life of the mice and the duration of their illness. Motor function, as evaluated by a Rotarod performance, was improved in rhGAL-1/ox-treated mice. Significantly more anterior horn neurons of the lumbar and cervical cords were preserved in the mice injected with rhGAL-1/ox than in those injected with physiological saline. The study suggests that rhGAL-1/ox administration could be a new therapeutic strategy for ALS.

Original languageEnglish
Pages (from-to)203-211
Number of pages9
JournalExperimental Neurology
Volume194
Issue number1
DOIs
Publication statusPublished - 2005 Jul 1

Keywords

  • Amyotrophic lateral sclerosis
  • Cu/Zn superoxide dismutase
  • Oxidized galectin-1
  • Transgenic mice

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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    Chang-Hong, R., Wada, M., Koyama, S., Kimura, H., Arawaka, S., Kawanami, T., Kurita, K., Kadoya, T., Aoki, M., Itoyama, Y., & Kato, T. (2005). Neuroprotective effect of oxidized galectin-1 in a transgenic mouse model of amyotrophic lateral sclerosis. Experimental Neurology, 194(1), 203-211. https://doi.org/10.1016/j.expneurol.2005.02.011