The project focuses on the nucleoli of neurons.
Óscar Fernández Capetillo, from the National Cancer Research Center in Madrid (CNIO), is exploring how to improve the treatment of amyotrophic lateral sclerosis (ALS). He does it with a different approach than usual, which had largely focused on the SOD1 gene, involved in oxidative stress.
“Given that the treatments based on the investigations of this gene have not given very encouraging results, we explored the therapeutic possibilities offered by mutations in other genes. We are making progress in understanding what the underlying problem is that leads to the death of neurons in these patients and the disease to occur”, comments Fernández-Capetillo. “A possible cause of the degeneration of neurons caused by ALS is a general problem of RNA accessibility, which is essential for cells to make proteins from their genetic material,” he details.
His research focuses on gene mutations involved in RNA metabolism, and also how they affect cell nucleoli, structures that accumulate ribosomal RNA. “In samples from patients with various neurodegenerative diseases, it has been observed that neurons have fragmented or deformed nucleoli, a sign that the ribosomes have not just been created and, therefore, neither have the proteins. We do not know if it is the cause of the degeneration of neurons, but we do know that it is linked, and that, when the ribosomes do not work, the effect is lethal for the cells”, specifies the scientist.
Taking advantage of the experience of another laboratory directed by Fernández-Capetillo at the Karolinska Institute, the researchers have screened drugs to identify compounds that mitigate the nucleolar problems associated with ALS mutations. They have a list of candidates and have tested some in cells in the laboratory and in the fruit fly, with good results. Isabel Troytino