Amyotrophic Lateral Sclerosis (cont.)
What causes ALS?
The cause of ALS is not known, and scientists do not yet
know why ALS strikes some people and not others. An important step toward
answering that question came in 1993 when scientists supported by the National
Institute of Neurological Disorders and Stroke (NINDS) discovered that mutations in the gene that produces
the SOD1 enzyme were associated with some cases of familial ALS. This enzyme is
a powerful antioxidant that protects the body from damage caused by free
radicals. Free radicals are highly reactive molecules produced by cells during
normal metabolism. If not neutralized, free radicals can accumulate and cause
random damage to the DNA and proteins within cells. Although it is not yet clear
how the SOD1 gene mutation leads to motor neuron degeneration, researchers have
theorized that an accumulation of free radicals may result from the faulty
functioning of this gene. In support of this, animal studies have shown that
motor neuron degeneration and deficits in motor function accompany the presence
of the SOD1 mutation.
Studies also have focused on the role of glutamate in motor neuron
degeneration. Glutamate is one of the chemical messengers or neurotransmitters
in the brain. Scientists have found that, compared to healthy people, ALS
patients have higher levels of glutamate in the serum and spinal fluid.
Laboratory studies have demonstrated that neurons begin to die off when they are
exposed over long periods to excessive amounts of glutamate. Now, scientists are
trying to understand what mechanisms lead to a buildup of unneeded glutamate in
the spinal fluid and how this imbalance could contribute to the development of
ALS.
Autoimmune responses—which occur when the body's immune system attacks normal
cells - have been suggested as one possible cause for motor neuron degeneration in
ALS. Some scientists theorize that antibodies may directly or indirectly impair
the function of motor neurons, interfering with the transmission of signals
between the brain and muscles.
In searching for the cause of ALS, researchers have also studied
environmental factors such as exposure to toxic or infectious agents. Other
research has examined the possible role of dietary deficiency or trauma.
However, as of yet, there is insufficient evidence to implicate these factors as
causes of ALS.
Future research may show that many factors, including a genetic
predisposition, are involved in the development of ALS.
Next: How is ALS treated? »
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