The Study Of Oxidative Stress In Immune-mediated Spinal Cord Motoneuron Destruction

Charcot first described amyotrophic lateral sclerosis (ALS) in 1869.This creeping disorder ,known colloquially as Lou Gehrig's disease, is a chronic lethal neurodegenerative disease characterized by the progressive loss of motor neurons in the cortex,brainstem,and spinal cord.,leading to profound weakness and atrophy of muscles.Most patients die of respiratory failure within 3 to 5 years after symptoms onset.From its stigmata of episode and heredity,ALS can be divided into familial amyotrophic lateral sclerosis (FALS) and sporadic amyotrophic lateral sclerosis (SALS).FALS is less than 10% of the total ALS patients, while SALS is more than 90%. FALS is mainly caused by the mutation of copper/zinc superoxide dismutase (Cu/Zn SOD) gene, whose site is at 21q22.1～22.2. This suggests that FALS should be a kind of genetic disease. The etiology of SALS, which accounts for the majority of all ALS cases, remains to be resolved, and several pathogenic mechanisms may beinvolved:(1)excitotoxicity,(2)oxidativestress,(3)autoimmunity,(4)mitochon- dria dysfunction, (5) over phosphorylation of neurofilament , (6) deficiency of neurotrophic factors,et al.Despite significant advances in our understanding of the pathogenesis of motor neuron degeneration,ALS remains one of the most catastrophic diseases of our aging population. Riluzole, the only drug launched for treatment ALS by FDA may only slow disease progression.Truly effective therapy is not currently available for the disease Autopsy materials offer only about end-stage changes.We can not investigate the early changes of ALS.So it is very necessary to established ALS models.At present,the study is mainly focused on culture models in vitro and SOD1 transgenic mice models.Traditional motor neuron culture is another model. Its virtue is little interference. We can observe the form and function changes...