Researchers atthe Babraham Institute and University of Massachusetts Medical School inthe United States have developed a new model to study motor neuron degeneration.
The work has already been used to identifythree genes involved in the neurodegeneration process. According to the team, the findings could have relevance for understanding the progression of amyotrophic lateral sclerosis (ALS) and otherforms of motor neuron disease (MND). ALS is the most common form of adult-onset motor neuron disease and kills more than 1,200 people a year in the UK alone. The researchers developed a new model to study neurodegeneration in the common fruit fly (Drosophila melanogaster). In contrast to other methods used to studyneurodegeneration such as looking at changesin eye morphology or studying larval stages, the researchers focused their attention on studying the neurons in a fruit fly’s leg. Using the leg allows the detailed study of asingle motor neuron, the nerve cell involved in passing signals from the brain to a muscle.
The model permits genuine ageing studiesto take place as changes in neurons can beobserved in flies of different ages. The adult fruit fly can live for more than two months in the lab. Furthermore, the fly provides the benefits of rapid development (ten days from egg to adult), allowing high- throughput genetic screens. The researchers used the new model to study the role of a protein central to the development of ALS called TDP-43. Exposing flies to a mutagen and looking forreduced neurodegeneration in their offspringallowed researchers to identify three genesimplicated in mediating the effects of TDP-43. One, shaggy/GSK3, was already known to be associated with the neurodegeneration process but two of them, hat-trickand xmas-2, were new discoveries. Dr Jemeen Sreedharan, Senior Research Fellow in the signalling research programme at the Babraham Institute and lead author on the paper which the team wrote on their findings, said:“We’re extremely excited about our new approach to using the power of Drosophilagenetics. “Never before has anyone been able to studyadult neurodegeneration in an invertebrate system with such ease.
“By modelling the earliest stages of ALS, synaptic and axon degeneration, we have identified three intriguing genetic suppressorsof degeneration in the fly and are now validating these results in mammalian neuronal cultures. We hope that by usingthe fly we can accelerate progress towards eventually developing therapies for ALS andother neurodegenerative diseases.” Funding for the research was provided by theMedical Research Council, a Motor Neurone Disease Association Lady Edith Wolfson Fellowship and the Max Rosenfeld Fund.