TDP-43 in motor neuron disease formation in Drosophila

Description:

What this research means to you: Recent research has led scientists to believe that a protein called TDP-43 may be involved in the development of MND. This project will use fruitflies to investigate how problems with TDP-43 affect motor neurons and aims to clarify the role of TDP-43 in the underlying mechanism of MND; this may eventually guide the development of new treatment strategies.

The researchers explain in more detail: Abnormal clumps of proteins are a typical feature of degenerating motor neurones in MND. Scientists recently discovered that a protein called TDP-43 was included in the clumps found in most cases of MND and that pieces of TDP-43 accumulate in affected motor neurones.
In the past few years, the fruitfly Drosophila melanogaster has been shown to be a good model system for studying various neurological diseases. This project aims to use the fruitfly to understand more about how problems with TDP-43 might contribute to the disease process in MND. TDP-43 dysfunction will be re-created in the fly through accumulation of fragments of human TDP-43 in the fly’s central nervous system. We will also inactivate the genes for the fly’s own versions of TDP-43. We will then analyse the effects of doing this on the fly in terms of motor neurone degeneration, movement problems and decreased life span.
We expect to determine any causal relationship between TDP-43 dysfunction and motor neuron degeneration in Drosophila which will immediately lead to fundamental insights into the role of TDP-43 in the development of MND. This in turn can directly guide clinical research into TDP-43-related MND, and the development of novel therapeutic strategies.