SOD1

The SOD1 gene provides instructions for making an enzyme called superoxide dismutase that is abundant in cells throughout the body. This enzyme neutralizes supercharged oxygen molecules (superoxide radicals), which can damage cells if their levels are not controlled. Superoxide radicals are byproducts of normal cell processes, particularly energy-producing reactions that occur in specialized structures called mitochondria. To function properly, the superoxide dismutase enzyme must bind to copper and zinc.

amyotrophic lateral sclerosis - caused by mutations in the SOD1 gene

More than 100 SOD1 mutations that cause type 1 amyotrophic lateral sclerosis have been identified. Most of these mutations change one of the building blocks (amino acids) used to make the enzyme superoxide dismutase. The most common mutation among Americans with type 1 amyotrophic lateral sclerosis replaces the amino acid alanine with the amino acid valine at position 4 in the enzyme. (This mutation is written as Ala4Val or A4V). Other types of mutations result in an enzyme of abnormal size.

The superoxide dismutase enzyme probably gains new, but harmful, properties when altered by SOD1 mutations. It is unclear why nerve cells in the brain and spinal cord that control muscle movement (motor neurons) are particularly sensitive to SOD1 mutations. Researchers have suggested several ways in which the altered enzyme may cause the death of motor neurons. These possibilities include an accumulation of harmful superoxide radicals, increased production of other types of toxic radicals, abnormal mitochondria that cannot meet the high energy demands of motor neurons, promotion of cell suicide (apoptosis), formation of clumps (aggregates) of misfolded superoxide dismutase that are toxic, or the continued stimulation of nerve cells that causes them to burn out and die (excitotoxicity).