What goes wrong in motor neurones?
Investigating how these factors can cause MND and could provide researchers with therapeutic targets.
Faulty scaffolding. Cellular ‘scaffolding’, called the cytoskeleton ensures that the shape and structure of motor neurones and other cells is maintained. If the structure is not held, it could cause the cell to degenerate.
Editors on strike. ‘Editors’ copy, tidy and transport short sections of code, known as RNA, to produce instructions that can then be used to build proteins.. If this process becomes faulty, then the production of proteins could be adversely affected and cause MND.
Disruption to chemical communication networks. Electrical messages are transmitted from one motor neurone to the next via the release of a chemical messenger in the gap between them. For many motor neurones this chemical messenger is glutamate but at high concentrations glutamate can be toxic.
Transport disruption. Motor neurones are large cells, the largest of which can be up to a metre long. It is important that their transport systems for moving nutrients, waste and components from one end to the other work well.
Aggregation. Abnormal clumps (aggregates) of protein molecules are found inside motor neurones affected by MND and may disrupt their normal functioning.
Build up of toxic waste. Oxygen free radicals are toxic chemicals formed as a normal by-product of processes within the cell. They are normally mopped up by antioxidants, but research suggests that in MND, the motor neurones’ own antioxidant defence pathways may be suppressed leading to a toxic build-up of waste.
Power failure. All cells contain tiny ‘batteries’ called mitochondria, which are responsible for producing energy for the cell and also play other key roles in maintaining the cell’s normal function. The mitochondria in motor neurones from people with MND appear abnormal.
Lack of nerve nourishing factors. There is some evidence that motor neurones become more susceptible to MND because of the lack of nutrients. One form of motor neurone nutrients are a group of chemicals called neurotrophic factors, literally meaning ‘nerve nourishing factors’.
Problem neighbours. Motor neurones are surrounded by cells called glia, which normally provide the neurones with support and nourishment. However, researchers have now come to realise that glial cells, such as oligodendrocytes, can in fact contribute to motor neurone degeneration. These cells may lose their supportive properties and can even become toxic.
*Image kindly provided by Dr Karla Miller, University of Oxford