Motor neurone disease - Causes of motor neurone disease

Motor neurone disease occurs when motor neurones progressively lose their function. It is not clear why this happens.

In most cases, a person with motor neurone disease will not have a family history of the condition. This is known as sporadic motor neurone disease. Researchers believe that the cause is probably a combination of genetic and environmental factors that build up throughout life.

However, about 5% of people with motor neurone disease have a close family relative who also has the condition or the related condition frontotemporal dementia. This is called familial motor neurone disease and is more closely linked to a problem with genes.

Possible causes of motor neurone disease

It's still unclear why the motor neurones begin to lose function. Most experts believe that the loss of function is caused by a combination of interrelated factors that affect your cells, some of which are outlined below.

Glutamate

Nerve cells use special "messenger chemicals" called neurotransmitters to transmit information from one cell to another. One of the neurotransmitters is called glutamate. There is 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 is not linked to dietary intake of glutamate.

Cell disruption

All cells contain transport systems that move nutrients and other chemicals into the cell while moving waste products out of the cell. Research suggests that the transport systems in motor neurones become disrupted in motor neurone disease. This may contribute to the loss of normal nerve function.

Aggregates

Aggregates are abnormal clumps of protein that develop inside motor neurones. They have been found in most cases of motor neurone disease. The clumps may disrupt the normal working of the motor neurones.

Toxic waste

Toxic waste can build up in cells over time as a natural by-product of normal cell activity, just as using a cooker repeatedly can cause grease to build up inside it. The body gets rid of the toxic waste by producing substances known as antioxidants. Research suggests that in motor neurone disease the motor neurones may be deficient in antioxidants, but there is no evidence that this is because of poor dietary intake.

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 appear to be abnormal.

Lack of nutrients

Like all living tissue, motor neurones need a regular supply of nutrients. Motor neurones receive nutrients from a group of proteins known as neurotrophic factors. There's evidence that in motor neurone disease neurotrophic factors are not produced in the correct way. This may make the motor neurones more vulnerable to damage and affect their function.

Glia cells

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

Familial motor neurone disease

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

A genetic mutation is when the instructions carried in all living cells become scrambled in some way. This means that one or more processes of the body don't work properly. See genetics for more information.

So far, four major genetic mutations have been identified in the 5% of patients 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, TDP-43 and FUS.

If your father, mother, sister or brother developed motor neurone disease and there is another family member with either motor neurone disease or frontotemporal dementia, you have a 50% chance of carrying the same gene. However, this does not mean you will definitely develop the disease.

If you have motor neurone disease and there is no wider family history, the overall risk to your own children is currently thought to be very 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.