Question

Mutations in SOD are associated with the neurodegenerative disease amyotrophic lateral sclerosis ALS. Explain why researchers initially believed that loss of SOD activity would damage neurons.

Short answer

Increased reactive oxygen species (ROS) levels increase cell mitochondrial oxidative damage. This is the reason researchers initially believed that loss of SOD activity would damage neurons as SOD protects the cell from ROS.

Step-by-step solution

Action of SOD

SODs are a family of enzymes that catalyze the dismutation of superoxide radicals O₂^-to molecular oxygen (O₂)and hydrogen peroxide (H₂O₂), providing cellular protection against reactive oxygen species.SOD (Superoxide dismutase) enzymes are found in almost all cells. The reaction catalyzed by SOD is as follows:

$2{\mathrm{O}}_2^{-}+2{\mathrm{H}}^{+}\to {\mathrm{H}}_2{\mathrm{O}}_2+{\mathrm{O}}_2$

The H₂O₂ released are then removed by catalase and glutathione peroxidase.

Effect of SOD on neurons

An increased mitochondrial oxidative damage in cells is caused by an increase in reactive oxygen species (ROS). This damage occurs in neurons as well. SOD defends the cell against oxidative stress.

If there is a deficiency in proteins involved in the electron transport chain or a mutation in glucose-6-phosphate dehydrogenase, oxy radicals can be created. Moreover, oxy radicals will increase if SOD is altered. Thus, the cell is negatively affected by oxy radicals.

If SOD mutations are found in neurons, the neurons will stop working. As a result, researchers first assumed that a decrease in SOD activity would harm neurons.