Galectin-1 as a potential therapeutic agent for amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects almost selectively motor neurons in the central nervous system. Most ALS patients die within five years of onset. One of the neuropathological features of ALS is an "axonal spheroid," a large swelling of a motor axon within the anterior horn of the spinal cord; this abnormal structure seems to be related to the pathogenesis of motor neuron degeneration in ALS. In 2001, using biochemical and immunohistochemical methods, we found an accumulation of galectin-1 in ALS spheroids. By immuno-electron microscopy, the galectin-1 accumulated in the spheroids was observed to be closely associated with neurofilaments. Furthermore, we observed a marked depletion of galectin-1 in the skin of ALS patients; another abnormality frequently observed in ALS. These findings, therefore, suggest that galectin-1 may be involved in the pathogenesis of ALS. It is known that an oxidized form of galectin-1 promotes axonal regeneration; however, it is not known whether oxidized galectin-1 has a beneficial or an adverse effect on the pathophysiology of ALS. To examine this issue, we administered oxidized galectin-1 to transgenic mice with H46R mutant SOD1, an ALS model mouse. The results showed that the administration of oxidized galectin-1 improved the motor activity, delayed the onset of symptoms, and prolonged the survival of the galectin-1-treated mice. Furthermore, the number of remaining motor neurons in the spinal cord was more preserved in the galectin-1-treated mice than in the non-treated mice. We conclude that galectin-1 could be a candidate agent for the treatment of ALS.
Kato
T
T
Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology (DNHMED), Yamagata University School of Medicine, Japan. tkato@med.id.yamagata-u.ac.jp
Ren
C-H
CH
Wada
M
M
Kawanami
T
T
D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D037483:Galectin 1 / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D018696:Neuroprotective Agents / Q000494:pharmacology
D037483:Galectin 1; D018696:Neuroprotective Agents