by Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a devastating neurodegenerative disorder that progressively impairs muscle control due to the death of neurons in the brain and spinal cord. Unfortunately, there is currently no cure for ALS. However, a recent study conducted by the University of Barcelona offers new hope for the treatment of this debilitating disease.
The study focuses on a specific aspect of ALS: the mutation in the C9orf72 gene, which is present in approximately 33% of familial ALS cases and 5% of sporadic ALS cases in Spain. This genetic mutation leads to the production of dipeptides with a high number of positive charges, which have proven to be highly toxic to motor neurons.
To better understand the molecular mechanisms behind the toxic effects of these dipeptides, the researchers employed a combination of computational and experimental techniques. Their findings revealed that the toxicity of the dipeptides is partly caused by their binding to ribosomal RNA (rRNA), a fundamental molecule involved in protein synthesis in cells.
Armed with this knowledge, the researchers developed an innovative strategy to counteract the toxic effects of the dipeptides. They designed a molecular trap that mimicked the specific rRNA sequence to which the dipeptides bind during the pathological process. The goal was to prevent the dipeptides from exerting their neurotoxic effects by redirecting them to the trap.
To test the effectiveness of their strategy, the researchers conducted experiments using neurons derived from patient tissue in vitro, as well as an in vivo model of the disease using vinegar flies. The results were promising, as the molecular trap successfully reduced defects in ribosome biosynthesis and toxicity in cells expressing the dipeptides. Furthermore, the trap prevented the death of motor neurons in ALS patients with mutations in the C9orf72 gene.
While further research is needed to fully validate and understand the mechanisms of this strategy, the researchers believe that their findings represent a significant step forward in the treatment of ALS. They assert that the use of RNA traps has the potential to not only study RNA-protein interactions but also protect neurons from the harmful effects of abnormal proteins in other neurodegenerative diseases.
The study, published in the journal Science Advances, marks an important milestone in the quest to find a treatment for ALS. By targeting the toxic effects of specific dipeptides, the researchers have demonstrated the potential of their molecular trap strategy to reduce neuron death and alleviate the symptoms of ALS. This breakthrough brings hope to the millions of individuals and families affected by this devastating disease.
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- Source: Coherent Market Insights, Public sources, Desk research
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