A research group, directed by Alessandro Rosa, scientific coordinator of the "StressFus" project and researcher at the Department of Biology and Biotechnology Charles Darwin in collaboration with the Italian Institute of Technology, has studied the impact of the mutation in the FUS gene, using as a model, motor neurons derived from induced pluripotent stem cells (iPSC, induced pluripotent stem cells) acquired from ALS patients. The project, funded by the AriSLA Foundation through the 2016 Call for Proposals, aimed at investigating the not yet fully understood mechanisms underlying the degeneration of motor neurons (the nerve cells mainly affected by ALS) caused by mutations in the TDP-43 and FUS genes. Mutations in these genes intervene, at various levels, to alter the production of proteins capable of binding RNA, a molecule involved in various biological roles of coding, decoding, regulation and expression of genes. The results have been published on "Scientific Reports" Journal (Nature publishing group). In the paper, the authors explain how a specific mutation in the FUS gene associated with particularly aggressive forms of ALS can have important effects on the proteome, i.e. all the proteins present in the cell.

"The mechanism underlying the alteration of the proteome - says Alessandro Rosa - seems to involve the aberrant binding of the mutated FUS protein to a particular region of the messenger RNA (a molecule responsible for encoding information from DNA into protein), called 3'UTR. The most important effect is on proteins, a necessary element the cells need to effectively respond to oxidative stress and on proteins that make up the cytoskeleton, the internal scaffolding of the motor neuron".

Based on these results, further studies aimed at understanding the link between cytoskeletal alteration and motor neuron degeneration in patients with a mutation in the FUS gene will continue.

AriSLA, Italian Research Foundation for Amyotrophic Lateral Sclerosis (ALS) supports scientific research of excellence on ALS aimed at effectively "defeating" this very serious disease, still incurable that in Italy alone involves about 6000 people.