title: L-carnitine suppresses the onset of neuromuscular degeneration and increases the life span of mice with familial amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal disease caused by progressive degeneration of motor neurons in the spinal cord and motor cortex. Although the etiology of ALS remains unknown, a mutation of the gene encoding Cu,Zn-superoxide dismutase (SOD1) has been reported in 20% of familial cases of ALS (FALS). Transgenic mice that overexpress a mutated human SOD1 exhibit a phenotype and pathology similar to those observed in patients with FALS. Mitochondrial abnormality has been reported in patients with ALS and in animal models of FALS. We recently reported that L-carnitine, an essential cofactor for the beta-oxidation of long-chain fatty acids, effectively inhibits various types of mitochondrial injury and apoptosis both in vitro and in vivo. The present study demonstrates that oral administration of L-carnitine prior to disease onset significantly delayed the onset of signs of disease (log-rank P=0.0008), delayed deterioration of motor activity, and extended life span (log-rank P=0.0001) in transgenic mice carrying a human SOD1 gene with a G93A mutation (Tg). More importantly, subcutaneous injection of L-carnitine increased the life span of Tg mice (46% increase in male, 60% increase in female) even when given after the appearance of signs of disease.
authors.affiliation: Department of Biochemistry and Molecular Pathology, Osaka City University Medical School, Osaka 545-8585, Japan.
authors.forename: Yukimi
authors.initials: Y
authors.lastname: Kira
authors.forename: Manabu
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Akemi
authors.initials: A
authors.lastname: Ochi
authors.forename: Eisuke
authors.initials: E
authors.lastname: Sato
authors.forename: Masayasu
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000225:Adenine; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002331:Carnitine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D018450:Disease Progression; D005260:Female; D006147:Guanine; D006614:Hindlimb; D006801:Humans; D007279:Injections, Subcutaneous; D008136:Longevity / Q000187:drug effects*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009154:Mutation; D009410:Nerve Degeneration / Q000517:prevention & control*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C000606290:SOD1 protein, human; D014803:Vitamin B Complex; D006147:Guanine; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000225:Adenine; D002331:Carnitine