SOD1

The SOD1 gene provides instructions for making an enzyme called superoxide dismutase, which is abundant in cells throughout the body. This enzyme attaches (binds) to molecules of copper and zinc to break down toxic, charged oxygen molecules called superoxide radicals. Superoxide radicals can damage cells if too many accumulate within cells. Superoxide radicals are byproducts of normal cell processes, particularly energy-producing reactions, and must be broken down regularly.

amyotrophic lateral sclerosis - caused by mutations in the SOD1 gene

At least 170 mutations in the SOD1 gene have been found to cause amyotrophic lateral sclerosis (ALS), a condition characterized by progressive movement problems and muscle wasting. Most of these mutations change one of the protein building blocks (amino acids) in the superoxide dismutase enzyme. About half of all Americans with ALS caused by SOD1 gene mutations have a particular mutation that replaces the amino acid alanine with the amino acid valine at position 4 in the enzyme. (This mutation is written as Ala4Val or A4V.) The A4V mutation is typically associated with more severe signs and symptoms.

The superoxide dismutase enzyme probably gains new, but harmful, properties when altered by SOD1 gene mutations. It is unclear why the nerve cells that control muscle movement, which are affected in ALS, are particularly sensitive to SOD1 gene mutations. Researchers have suggested several ways in which the altered enzyme may cause the death of nerve cells. These possibilities include an accumulation of harmful superoxide radicals, increased production of other types of toxic radicals, increased cell death, or formation of clumps (aggregates) of misfolded superoxide dismutase that may be toxic to cells.