Mitochondrial redox dysfunction in MND: a therapeutic role for the peroxiredoxins

Description:

What this research means to you: A number of mechanisms appear to contribute to motor neurone damage. This project will investigate a protein called Prx 3 that may have a role in limiting the effects of some of these harmful mechanisms. The researchers will use cell and animal models of MND to see whether manipulating Prx3 can protect motor neurones; if so, this could lead to the development of new drugs.

The research explains in more detail: No single theory is yet able to explain everything we see happening in the motor neurones of patients with MND. Leading contenders include oxidative stress (damage caused to motor neurones by oxygen free-radicals, unavoidable by-products of our metabolism); protein aggregation where proteins in motor neurones clump together; and lastly, problems with the mitochondria, the power stations of the cell which allow food to be converted to energy.
In our earlier work we showed a reduction in the level of a protein called peroxiredoxin 3 (Prx 3) in MND. Prx 3 is a protein found in the mitochondria that protects against oxidative stress and may also act to reduce protein aggregation. We want to investigate whether changes in the amount and activity of this protein can protect the motor neurone from the damage that happens in MND. We think that introducing more of this protein into the mitochondria of motor neurones may be protective. We also suspect that if we can increase the anti-oxidant activity of Prx 3 that this too may protect the motor neurone. We want to test these ideas in motor neuronal cells grown up in the laboratory and in mice genetically-modified to develop a disease very similar to MND in humans. If our theories prove to be correct we plan to look at drugs already used safely in humans to see if any of them can bring about the same beneficial changes in the level and activity of Prx 3 in our motor neuronal cells. Experiments like these are the earliest steps in the development of new MND drugs. Drugs that protect motor neuronal cells in the lab are tested in MND mice. If they succeed and prove safe they may then be tested in patients.