Pathological abnormalities associated with motor neuron disease have been identified using a new technique developed at the University of Birmingham.
The method will help scientists better understand the changes in the brain that lead to motor neuron disease (MND) and could ultimately provide insights that will help in the development of new treatments. The abnormalities were identified in a collaboration between the University of Birmingham and the University of Sheffield and have been published today [8 Aug] in Nature communication.
Motor neuron disease, also known as amyotrophic lateral sclerosis or ALS, is a muscle wasting caused by messages from the brain’s motor neurons not reaching the muscles, causing them to weaken. Around 5,000 people in Britain suffer from the disease at any one time and there is currently no cure.
At the University of Birmingham, researchers have developed a technique that allows them to examine specific proteins in their native state, directly from brain and spinal cord tissue samples. This instrument, called native ambient mass spectrometry (NAMS), allows the structure of proteins in relation to their location in tissue to be studied in more detail than ever before.
Working with colleagues from the University of Sheffield, they were able to identify a metal deficiency in a specific protein, known as SOD1, and show that it accumulates in specific parts of the brain and spinal cord in mice with MND.
SOD1 has been implicated in motor neuron diseases before, but this is the first time that detailed molecular imaging has been able to show how versions of the protein with missing metal ions accumulate in affected mice.
Lead researcher Helen Cooper from the Birmingham School of Biosciences said: “This approach is the first to demonstrate that this form of SOD1 correlates with the pathology of motor neuron disease. It is a very early step towards finding treatments for MND and is also an exciting new route for understanding the molecular basis of other diseases in unprecedented detail.”
We were very excited to apply this fantastic methodology that Helen’s team has developed to gain new insights into the biology of MND and we look forward to using the technology further to investigate why motor neurons die and to discover new interventions for people affected by MND.”
Richard Mead from the Sheffield Institute for Translational Neuroscience
The next steps for the researchers will be to test whether the same imbalances are present in human tissue samples, and to attempt to treat the imbalance in the mice using available drug compounds.
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Magazine reference:
Hale, P.B. et al. (2024). Mass spectrometry imaging of SOD1 protein-metal complexes in SOD1G93A transgenic mice implicates demetallation with pathology. Nature communication. doi.org/10.1038/s41467-024-50514-7.