Are cells' 'power houses' the key to MND?

The importance of mitochondria, the compartment within the cell that provides its energy, emerged as a hot topic at the Symposium.
In addition to the production of energy for the cell, mitcohondria have several other functions, including maintaining a biochemical balance within the cell and triggering cell death. Mitochondria are a unique as they contain their own DNA – known as mitochondrial DNA. This is entirely separate from the rest of the DNA within the cell, which is held in a compartment known as the ‘nucleus’.

A closer look at mitochondria DNA

In his overview of this area of research Dr Douglas Wallace (Irvine, California) explained that mitochondrial DNA has many roles in the body, ranging from determining lifespan (the lifespan of many species can be determined by looking at the level of damage in mitochondrial DNA), to evolving protective genetic variations to different environmental conditions. Specific variations in mitochondrial DNA have also been to shown to be risk factors for other neurodegenerative diseases. Their role in MND remains to be understood.

Preventing cell death

One theory is that the body’s system for cell death, an essential and necessary part of healthy tissues, is over-triggered in MND. Dr Jochen Prehn of Royal College of Surgeons in Ireland, presented some work investigating the effects of genetically modifying the pathways leading to this cell death trigger and how this would affect motor neurones in MND. His preliminary work suggests that such an approach may delay motor neurone degeneration in animal models of MND.

The following presentation by Dr Wood-Allum of Sheffield University, the result of many careful and painstaking years of work, suggested that in MND there may be lower than normal levels of the protective mechanisms to prevent cell death from being triggered. By restoring these to their normal level, the effects of motor neurone degeneration may be reduced.

Location of energy supplies...

In the final presentation in this session, Dr Sue Browne based at Cornell University, New York asked whether defects much earlier in the energy production pathway contribute to motor neurone death – in the provision of the fuel for the mitochondria. She described a timeline of energy shortage. In very young mice affected by a rare, inherited form of MND, levels of the cells’ easily available energy (‘ATP’) were reduced in the brain, 30 days later, still before the onset of symptoms of MND were found, levels of the fuel for energy production – glucose – were reduced in the brain. It was only much later in the course of the disease in these animals that reductions in glucose were seen in spinal cord motor neurones.