Pyruvate slows disease progression in a G93A SOD1 mutant transgenic mouse model.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by selective motor neuron death, and currently no effective treatment is available for ALS. In this study, we investigated the neuroprotective effects of pyruvate, which acts as an anti-oxidant and as an energy source. We treated G93A SOD1 transgenic mice with pyruvate (from 70 days of age, i.p., at 1000 mg/kg/week), and found that it prolonged average lifespan by 12.3 days (10.5%), slowed disease progression, and improved motor performance, but did not delay disease onset. Pyruvate treatment was also associated with reduced nitrotyrosine immunoreactivity, gliosis, and increased Bcl-2 expression in the spinal cords of G93A SOD1 transgenic mice. These results suggest that pyruvate treatment may be a potential therapeutic strategy in ALS.
Park
Jong-Ha
JH
Department of Neurology, Seoul National University College of Medicine, Clinical Research Institute of Seoul National University Hospital, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, South Korea.
Hong
Yoon-Ho
YH
Kim
Hyun-Jung
HJ
Kim
Sung-Min
SM
Kim
Min-Jeong
MJ
Park
Kyung-Seok
KS
Sung
Jung-Joon
JJ
Lee
Kwang-Woo
KW
D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005911:Gliosis / Q000188:drug therapy / Q000209:etiology; D051379:Mice; D008822:Mice, Transgenic; D011597:Psychomotor Performance / Q000187:drug effects; D019289:Pyruvic Acid / Q000627:therapeutic use*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics*; D016019:Survival Analysis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
C002744:3-nitrotyrosine; D014443:Tyrosine; D019289:Pyruvic Acid; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase