Proteinopathies

This session was dedicated to finding out more information on how proteins (which perform specific functions, such as transporting cargo from one place in a motor neurone to the other within the body) can cause MND.

The major highlight of this session was learning that the clumping (aggregation) of faulty proteins in the motor neurones of people with MND is also found in many other neurodegenerative diseases such as Alzheimer’s disease and Fronto-Temporal Dementia (FTD). This suggests that there is a common mechanism in the aggregation of faulty proteins in these diseases.

Two previously identified protein aggregates that may cause MND are called FUS and TDP-43. Interestingly, the build up of these specific faulty proteins is also found in FTD – this suggests that these two diseases are part of the same spectrum. This is also reiterated in that it is thought that 10-15% of people with MND will also be diagnosed with FTD (either before or after the diagnosis of MND). There is also evidence to suggest that up to 50% of people with MND will also have some degree of cognitive change through the progression of MND.

However, it is still important to determine why these proteins are becoming faulty and aggregating in motor neurones and what the exact disease causing mechanism is. The current feeling, said Prof Neumann, is that MND could either be caused (or contributed to) by either the loss of function of these proteins from the control centre of the cell (the nucleus) or by a toxic effect from the proteins not being able to transport themselves back to the control centre. Whether the true answer is one of these, something completely different, or indeed both is still to be determined.

If we can learn more about how proteins such as FUS and TDP-43 play a role in the development of MND, we will be able to identify suitable therapeutic targets so that future therapies can be developed with the hope of a new treatment for MND.