Amyotrophic lateral sclerosis

From Science Online

Contents 1 Also Known As Lou Gehrig's Disese 2 Biochemistry 3 Symptoms 4 Treatment

Also Known As Lou Gehrig's Disese

Though it is more commonly called Lou Gehrig's disease the medical name of this disease is Amyotrophic lateral sclerosis (ALS). ALS is a progressive neurodegenerative disease. That means that it directly effects neurons and causes the degeneration of cortical and spinal motor neurons. Those motor neurons are also connected to the brain and also to the muscles. When those neurons are damaged the brain can no longer control those muscles and that caused many problems. Once control is lost muscles will start to deteriorate and atrophy. There are two types of ALS, sporadic and familial. Roughly 5-10% of ASL cases are familial, the rest are sporadic.

(The ALS Association) (Miriam, 2007)

Biochemistry

The main protein that is involved with Amyotrophic lateral sclerosis is superoxide dismutase 1. SOD1, in its normal function, is the gene that contains the genetic code to make the enzyme superoxide dismutase. That enzyme is common through out the body and can be found in cell parts such as the cytosol, nucleus, peroxisomes, and mitochondrial intermembrane space. The main purpose of this enzyme is to neutralize superoxide radicals. Superoxide radicals are charged oxygen molecules, and they are common with cells, but if the level is not controlled cells can easily be damaged. Normal forms of this enzyme must bond to copper or zinc to be able to control the level of superoxide radicals in the body.

This is the reaction that takes place:

This structure is the mutated version of SOD1. It contains two alpha helices and five beta sheets. A normal SOD1 contains the amino acid alanine in position four. But when it is mutated the alanine is replaced by the amino acid valine, Ala4Val or A4V. There are some other mutations that can take place, such as an oversized protein, but the mutation with valine is the most common one that causes Amyotrophic lateral sclerosis.There is not a clear cut answer as to how this mutation causes Amyotrophic lateral sclerosis, but there are a few ideas. One of them would be that the efficiency at which the enzyme is decreased, and that results in more superoxide radicals.

There is another type of mutation, that one is common in familial ALS. G93A is the mutation where glycine is replaced by alanine in position 93.

Although those mutations are the most common, the ones that include SOD1, there are still cases where SOD1 mutations are not the cause. Those cases are still being worked on. One of the more recent discoveries is related to the amount of glutamate in the body. With normal amounts, glutamate is used to transfer information throughout the body. Though in post-mortum studies there is an increased amount of glutamate in the spinal fluids of ALS patients. The increased amount of glutamate causes the neurons to die and thus leads to ALS.

This protein is 2 COPPER, ZINC SUPEROXIDE DISMUTASE. There have been studies with this protein in trying to prevent some side effects of the illness and also how a mutation of the protein might be involved. There are 4 alpha helices in this protien along with 9 beta sheets. The helices and sheets determine the overall structure and the structure determines the function. 2SOD is has been used as a treatment for the illness by changing the mutated proteins for the correct ones (See treatment heading for more information.)

(Medical News Today) (Genetics Home Reference)

Symptoms

• Muscle weakness: hands, arms, legs or the muscles of speech, swallowing or breathing.
• Twitching and cramping of muscles, especially in the hands and feet. Muscle twitchings are called fasciculations.
• Impairment of the use of the arms and legs.
• "thick speech" and difficulty in projecting the voice.
• Advanced stages: shortness of breath, difficulty in breathing and swallowing.

Roughly 20,000 Americans currently have ALS, and 5,000 people are diagnosed every year. Most of the time the disease won’t show any signs till around the age of 40-60, but it can show sooner. Early symptoms are not the same for every one; this makes it much more difficult to diagnose ALS in early stages. Though there are some signs that early on can lead to ALS. One of those is developing problems with hands and feet. 60% of patients experience this in their early stages. Someone with an early stage of ASL may start to trip much more and have trouble carrying things. Eventually that weakness of the hands or feet will eventually spread to other parts of the body, leading to problems with speaking and breathing. Not everyone will experience the same progression of symptoms, but all will lead to eventual paralysis. It the the problems amd lack of control of breathing that usually causes those with ALS to die. The average survival time for someone with ALS is about three to five years, though that may vary. Because early symptoms can be so similar to other disorders, there are certain tests that can be done to give an idea if the patient does have ALS. Electromyography is the test that is commonly used. During Electromyography electrical activity is monitored in the muscles, a decline in activity might mean that the patient has ALS. Another test used is nerve conduction velocity. While this test does not give information if the patient has ALS, it will show if they have another disease with similar symptoms and thus ruling out ALS.

(The ALS Association)

(National Institute of Neurological Disorders and Stroke)

Treatment

There currently is not much in the lines of treatment for ALS, as well as no cure. Riluzole is a drug that has been approved by the FDA. Although it does not cure ALS, it works to reduce the amount of glutamate produced. Reducing the amount can prevent more damage and prolong the life of the patient by a couple of months, though riluzole can not reverse damage already done to neurons. The other treatments that are available are more to make the patient comfortable and make life a little easier. Things such as physical therapy can help the patient to maintain some movement and relieve pain. Speech therapy is also used for those who develop problems speaking. Scientists are currently working with variations of SOD1 to try and cure ALS. 2SOD is currently being worked on to try and level out copper and zinc levels and also to repair damaged DNA.

(National Institute of Neurological Disorders and Stroke)

(GIULIANO, 2007)

(, 2006)

References