Like a production line producing cars that don't work, motor neurones in MND produce proteins, including TDP-43, that pile up and accumulate at the end of the production line. These piles of junk proteins are a common feature of sporadic and familial forms of MND. A recent study conducted in Japan suggests that while researchers are looking for mistakes in the production of proteins it may be mistakes made earlier in the design of these molecules that cause the pile-ups. RNA is a molecule that is a messenger that carries the information from the blueprint in the gene to the machinery that will construct the protein product. Messenger RNA starts off its life as a full-length version of the original blueprint, however, it needs to be cropped or "spliced" in order to remove unnecessary information. This study headed by Yoshinori Nishimoto suggests that in the test tube, messenger RNA may not be "spliced" properly in the presence of mutant TDP-43.
In a direct test of the theory that the protein production line is faulty at the level between blue print and production line a research group led by Professor John Ravits in Seattle, USA has examined the spinal cords of sporadic MND tissue donors. In a world first Professor Ravits' team have shown that messenger RNA molecules from hundreds of different human genes are incorrectly "spliced". What this means is that proteins will be assembled from the wrong plans. So they are much more likely to either accumulate into piles of junk or not be produced at all. These errors were found to be specific to the area in and immediately around the motor neurones. Since these errors are found in motor neurones but not other distant parts of the spinal cord it may be a vital clue in solving the MND puzzle.
Linking sporadic MND with SOD1 familial MND is the work of Professor Michael Strong's laboratory in Ontario, Canada who have just shown that mutant SOD1 associated with some familial cases of MND can bind to RNA and stop it from interacting with the protein production machinery. This may mean that SOD1 may directly interact with some kinds of RNA slowing production of important proteins required for healthy neuron functioning.
Source: International MND research update -December 2009, Dr Justin Yerbury for MNDRIA