In This Issue

摘要

Copper-zinc superoxide dismutase (SOD1) is an antioxidant found in cytoplasm. Many different mutations in SOD1 have been linked to familial amyotrophic lateral sclerosis (ALS), arnneurodegenerative disease in which increasing motor neuron failure proves fatal. SOD1 aggregates have been found in human spinal cords during autopsies; in mice, similar aggregates are known to have a fibrillar nature characteristic of amyloid. Madhuri Chattopadhyay et al. studied the formation of SOD1 fibers in vitro and report that the initial nucle-ation that precedes fiber growth is accelerated under physiological conditions by an apo form of the dismutasern(SOD1 minus the copper and zinc ions it requires to function) in which a key disulfide bond is reduced. The authors found that only a small fraction of SOD1 needs to be reduced; once a nucleus has formed, SOD1 with intact disulfide bonds is recruited to the growing fiber. They also found that, to nucleate, SOD1 must possess key cysteine residues and that copper ions inhibit fiber formation more than do zinc ions. SOD1 mutants are known to be easily reduced, and the authors suggest that this, together with copper binding, could be the link between mutation and disease.