The Study On Mutant SOD1 Gene Associated Of An ALS Family Having A Unique Clinical Phenotype

BackgroundAmyotrophic lateral sclerosis(ALS) is a specific form of motor neuron diseases, a common denatured disease of nervous system, in which the upper and lower motor neurons are both invovled. It is a progressive neurodegenerative disorder, relentlessly progressive and most patients with this disease died of ball paralysis or pulmonary infection within five years of clinical onset. It has been found that ALS and other neurodegenerative disorders including Parkinson's disease, Huntington's disease, Alzheimer's disease and spinocerebellar ataxia have similar pathological menifestations, in which all lossed cells are dying of apoptosis, and insoluble protein aggregation is found in the inclusions in the dying neurons and astrocytes. Investigating one of these diseases thoroughly may provide evidences for the pathogenesis of these diseases and may be helpful to develop the rational strategies for minimizing or preventing the diseases. Though familial ALS(FALS) only accounts for 10%-20% of ALS, it may serve as an excellent model to identify an underlying gene defect responsible for motor neuron degeneration, for it has indistinguishable clinical and pathological expressions with sporadic ALS(SALS).Cytolic Cu/Zn superoxide dismutase(SOD1) is the main enzymie to catalyze the superoxide negative anion into H2O and O2 and remove its toxin in the cellular intracytoplasm. And SOD1 is the most important line of antioxidant enzyme defence system against reactive oxygen species(ROS), particularly superoxide anion radicals. It has been reported that mutations in the gene of SOD1 are responsible for 20% of cases of FALS. To date, more than 100 different heterozygous mutations in SOD1 have been found in patients with ALS, and all but one is dominant. Many of these mutations lead to the substitution of an amino acid within regions of the enzyme with very distinct structure and functional roles. It is thus fascinating to note that so many discrete SOD1 alternations share a similar clinical phenotype and there are only sublte differences in several fields. For example, in the cause of disease or the state of the illness, which indicates that FALS may...