ALS is a neurodegenerative disease that affects the upper motor neurons in the brain, and the lower motor neurons, which are in the spinal cord and brainstem. Upper motor neuron degeneration generally causes spasticity (tightness in a muscle), while lower motor neuron degeneration causes muscle weakness, muscle atrophy (shrinkage of muscles) and twitching.
ALS can familial, or inherited, which is passed from the parents to the children. Or the disease can appear sporadically — the type of ALS that doesn’t run in families often called “sporadic ALS.”
Familial ALS is very rare. Only about 5 to 10 percent of ALS cases are inherited, and it usually only requires one parent to carry the genetic mutation responsible for the disease. Mutations in more than a dozen genes have been found to cause familial ALS.
About 25 to 40 percent of all familial cases, however, is caused by a defect in a gene called “chromosome 9 open reading frame 72,” or C9ORF72. Some individuals with this genetic mutation may experience both motor neuron and dementia symptoms.
Another 12 to 20 percent of familial cases result from mutations in the gene that provides instructions for the production of the copper-zinc superoxide dismutase 1 (SOD1) enzyme that binds to copper and zinc molecules to break down toxic, charged oxygen molecules — called superoxide radicals — that are byproducts of normal cell processes. These molecules must be broken down regularly to avoid damaging cells. In cases where the SOD1 enzyme is not working properly, these molecules accumulate in nerve cells and cause their death, leading to ALS.
Most non-inherited ALS cases (90 percent or more) are considered to be sporadic. There appear to be genetic variations that influence one’s susceptibility to ALS, even if they don’t actually cause the disease.
Apart from genetic mutations, scientists have proposed other possible causes of non-inherited forms of ALS, including a chemical imbalance, an overactive immune response, and protein mishandling.
People with ALS generally have higher than normal levels of glutamate, a chemical messenger in the brain and in the spinal fluid around nerve cells. High levels of glutamate are toxic to some nerve cells and may cause ALS.
Overactive immune response
Sometimes a person’s immune system begins to attack healthy cells, which may lead to the death of nerve cells.
Mishandled proteins or proteins incorrectly processed, within the nerve cells may lead to a gradual accumulation of abnormal forms of these proteins in the cells, seriously damaging or directly killing them. Researchers believe that the inability of a protein system to repair nerve cells that tell the muscles what to do leads to ALS. This protein, called ubiquilin2, is involved in recycling damaged and misformed proteins in key nerve cells. In people with ALS, ubiquilin2 does not work as it should, leading to an accumulation of the damaged proteins and ubiquilin2 in critical nerve cells in the spinal cord and the brain.
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