MADRID, 20 (EUROPA PRESS)
A team of researchers led by Stockholm University (Sweden) has discovered why some nerve cells are more resistant to amyotrophic lateral sclerosis (ALS) and what happens to them when they are affected, providing greater insight into how to protect them against the disease.
"We have better understood how nerve cells can protect themselves against ALS. This opens up new targets for future therapies," said Eva Hedlund, the study's leader and professor of neurochemistry at Stockholm University.
The study, published in the journal 'Genome Research' and conducted in collaboration with the Paris Brain Institute (France) and Örebro University (Sweden), focused on a hereditary form of ALS caused by mutations in the SOD1 gene, in which resistant motor neurons do not respond significantly to the disease.
Among the main reasons for this resistance could be having "very high" basal levels of several nerve protective factors, such as Engrailed-1 (En1), Parvalbumin (Pvalb), Cd63, and Galanin (Gal). Notably, En1 functions as a "switch" for genes, controlling which proteins are produced in the cell.
"From previous research, we know that it can protect sensitive neurons from deterioration. But the fact that the protective factor is produced at such high levels in resistant motor neurons that control eye movements was a surprise," said one of the study's co-authors, Dr. Melanie Leboeuf.
Scientists have also found that sensitive motor neurons trigger both damaging and protective responses against ALS, activating genes such as En1, Pvalb, Cd63, and Gal, which are normally found at high levels in resistant cells.
They also detailed that these sensitive cells attempt to reestablish lost contact with the muscles by activating genes that promote regeneration, such as Atf3 and Sprr1a, although these attempts "ultimately fail."
The discovery of distinct basal and induced genetic activity in different nerve cells opens up new treatment possibilities, consisting of trying to stimulate cells to suppress negative responses and further stimulate those important for survival.
To gain a better understanding of which genetic responses in motor-sensitive neurons can be used to predict the disease, the team used machine learning techniques and artificial intelligence (AI). They were able to identify the genes VGF, INA, and PENK as strong predictors of the disease across different mutations, and as potential predictors for identifying ALS in human samples.
"We see the possibility that these genes could eventually be used as biomarkers for the disease and help with diagnosis and prognosis," explained Irene Mei, first author of the study and a doctoral student at the Department of Biomedical Sciences and Biophysics at Stockholm University.
