Good science shows the way. Highlight Commentary on 'Redox proteomics analysis of oxidatively modified proteins in G93A-SOD1 transgenic mice--a model of familial amyotrophic lateral sclerosis'.

摘要

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of pyramidal neurons in the motor cortex and motor neurons in the brain stem and spinal cord. There is no cure for ALS and patients typically die of respiratory failure between 1 and 5 years after diagnosis. The causes of ALS are unknown. Most of the cases are sporadic and 10% of the cases are hereditary (familial ALS) . In 1993, mutations in the gene for the antioxidant enzyme superoxide dismutase (SOD) were linked to 2-3% of the cases of familial ALS . These reports led to the oxidative stress hypothesis in ALS, which was first thought to be produced by a loss of function. Soon after, it became clear that the mutations were responsible for a gain of function. The mutant SOD gain-of-toxic-function hypothesis was based on the facts that some mutant enzymes had the same activity as wild-type SOD, mice deficient for SOD do not develop motor neuron disease, and mice transgenic for mutant, but not wild-type, SOD develop an ALS-like disease .