A team of researchers has shed light on the role of a certain protein in the development of amyotrophic lateral sclerosis (ALS), opening new treatment perspectives to slow down the neurodegenerative disease.
- The SOD1 protein, implicated in approximately 20% of cases of genetic ALS, is usually in the form of a dimer, but it can transform into a trimer, a three-unit structure that appears to acquire toxic properties for nerve cells. .
- The team of researchers found that trimers bind to different proteins depending on the tissue type, which could explain the complexity of ALS. “This suggests that there may be different mechanisms leading to cellular dysfunction and death, depending on the tissue or cell type.”
- This finding challenges the classic idea that muscle breakdown in ALS results solely from motor neuron degeneration.
There is currently no treatment to cure amyotrophic lateral sclerosis (ALS). A recent study carried out by a team of researchers from Penn State College of Medicine, in the United States, however, sheds new light on the role of a specific protein, superoxide dismutase 1 (SOD1), in the development and progression of neurodegenerative disease. This discovery, detailed in the journal Structurecould open the way to new therapeutic perspectives.
The role of SOD1 protein in ALS
The SOD1 protein, whose mutation is involved in approximately 20% of cases of ALS of genetic origin, usually appears in the form of a dimer, composed of two identical units. But under certain conditions, it can transform into a trimer, a three-unit structure that appears to acquire toxic properties for nerve cells. These trimers are linked to increased cell death in ALS models, but the exact molecular mechanisms still remain unclear.
To find out more, the team of researchers introduced these SOD1 trimers into mouse tissues, including the brain, spinal cord and muscles, to observe which proteins they interacted with. They found that trimers bind to different proteins depending on tissue type, which could explain the complexity of ALS.
In brain and spinal cord tissues, SOD1 trimers bind to proteins involved in neuron structure and communication, disrupting these essential functions. At the same time, they activate pathways linked to cellular aging, thus accelerating neuronal degeneration. In muscle tissue, they bind to proteins involved in metabolic processes, which can directly interfere with energy production in muscle cells.
“This suggests that there may be different mechanisms leading to cellular dysfunction and death, depending on the type of tissue or cell.”note one press release.
Towards new avenues of treatment against ALS
This finding challenges the classic idea that muscle breakdown in ALS results solely from motor neuron degeneration. Indeed, the study also reveals that in muscle cells, SOD1 trimers disrupt proteins involved in metabolism and energy production. These interactions could directly affect muscle function, leading to atrophy and thus contributing to disease progression.
Furthermore, the scientists also identified a new interaction between SOD1 trimers and the septin-7 protein, a key molecule in the structure and cellular communication of neurons. This protein, already associated with ALS in previous studies, could be disrupted by SOD1 trimers, causing neuronal degeneration. This new lead makes septin-7 a potential candidate for targeted therapies aimed at slowing the progression of the disease.