Causes of motor neurone disease

Motor neurone disease occurs whenspecialist nerve cells(motor neurones) in the brain and spinal cord progressively lose their function. It's not clear why this happens.

In most cases, a person with motor neurone disease won'thave a family history of the condition.This is known as sporadic motor neurone disease. Researchers believe that the cause is probably aseries of steps involving a mixture of damaging genetic and environmental factors.As we get older, we may gradually lose the ability to keep this damage under control, triggering irreversible neurodegeneration.

About 5% of people with motor neurone disease have a close family relative with the condition or a related condition known as frontotemporal dementia. This is called familial motor neurone disease which can be hereditary orlinked to a problem with genesthat can cause problems at a younger age.

Possible causes of motor neurone disease

It's still unclear why the motor neurones begin to lose function. Most experts believe that it's a combination of interrelated factors that ultimately affect either the motor neurones or the nerve cells that support them.

Aggregates and RNA processing

Aggregates are abnormal clumps of protein that develop inside motor neurones. They are found in nearly all cases of motor neurone disease and may disrupt the normal working of the motor neurones, or at least be a marker that the cell is under great strain.

The most common aggregate found is TDP-43, which is a very important protein involved in the correct processing of the genetic instructions for the cell through a molecule known as RNA.

Cell transport disruption

All cells contain transport systems that move nutrients and other chemicals into the cell and waste products out of the cell. Research suggests that the transport systems in motor neurones become disrupted. Over time, toxic waste can build up in cells as a natural by-product of normal cell activity.

The body gets rid of the toxic waste by producing substances known as antioxidants, and packaging the waste into containers called microvesicles. Research suggests that in motor neurone disease the motor neurones may be deficient in antioxidants. However, there's no evidence that this is due to poor dietary intake.

Glial cells

Glia are cells that surround and support motor neurones and provide them with nutrients. Glial cells also help relay information from one nerve cell to another.
Some cases of motor neurone disease may be caused by problems with the glial cells, which means that the motor neurones no longer receive the support and nutrition they need to function normally.

Glutamate

Nerve cells use special "messenger chemicals" called neurotransmitters to pass information from one cell to another. One of the neurotransmitters is called glutamate. There's evidence that the motor neurones in people with motor neurone disease may have become more sensitive to glutamate, resulting in damage to these cells. However, this isn't linked to dietary intake of glutamate.

Mitochondria

Mitochondria are the "batteries" of cells. They provide the energy that a cell needs to carry out its normal function. Research has shown that the mitochondria in the motor neurones of people with motor neurone disease seem to become abnormal.

Familial motor neurone disease

The fact that motor neurone disease can run in families suggests that single genetic mutations inherited from parents may sometimes have a much larger role in the condition.

A genetic mutation occurs when the instructions carried in cells become scrambled in some way. This results in one or more of the body's processes not working properly.

Four major genetic mutations have so far been identified in the 5% of people with a family history of motor neurone disease or the related condition, Frontotemporal dementia .

The largest group (about one third) have an expanded area of a gene called C9ORF72. Some people with this gene abnormality develop motor neurone disease, some develop frontotemporal dementia and some develop both. Other genes linked to familial motor neurone disease include SOD1, TARDBP and FUS.

If your father, mother, sister or brother developed motor neurone disease and were found to have one of these abnormal genes, you have a 50% chance of carrying the same gene. However, importantly, this doesn't necessarily mean you'll definitely developmotor neurone diseasein your lifetime.

If you've been diagnosed withmotor neurone disease but there's no wider family history, the overall risk to your own children is currently thought to be similar to that of the general population.

Genetic testing is available to determine whether you have one of the mutated genes associated with familial motor neurone disease. Your GP can give you more information about appropriate specialists who can help with the complex issue of when to perform genetic testing.