Motor neuronal protection by L-arginine prolongs survival of mutant SOD1 (G93A) ALS mice.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive paralysis due to motor neuron degeneration. Despite the fact that many different therapeutic strategies have been applied to prevent disease progression, no cure or effective therapy is currently available for ALS. We found that L-arginine protects cultured motor neurons from excitotoxic injury. We also found that L-arginine supplementation both prior to and after the onset of motor neuron degeneration in mtSOD1 (G93A) transgenic ALS mice significantly slowed the progression of neuropathology in lumbar spinal cord, delayed onset of motor dysfunction, and prolonged life span. Moreover, L-arginine treatment was associated with preservation of arginase I activity and neuroprotective polyamines in spinal cord motor neurons. Our findings show that L-arginine has potent in vitro and in vivo neuroprotective properties and may be a candidate for therapeutic trials in ALS.
Lee
Junghee
J
Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA. junghee@bu.edu
Ryu
Hoon
H
Kowall
Neil W
NW
D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D000818:Animals; D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000627:therapeutic use*; D019610:Cytoprotection; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009154:Mutation; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D013095:Spermidine / Q000276:immunology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
D018696:Neuroprotective Agents; D001120:Arginine; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D001119:Arginase; D013095:Spermidine