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Molecular origins of ALS
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Protein clumps associated with ALS arise from precarious protein levels in motor neurons found in the spinal cord.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that leads to muscle failure and is eventually fatal. It has been linked to clumps of apparently unrelated misfolded proteins, including SOD1, TDP-43, and FUS.
Now, a team including researchers from the University of Wollongong have created a list of all proteins found in ALS clumps and studied their concentrations in nerve cells. They found that, under normal physiological conditions, these otherwise unrelated proteins all exceed a critical concentration level in spinal motor neurons – nerve cells that control movement – that makes them more likely to cluster if the body can no longer balance protein levels as a result of ageing or disease.
The team generated a database that links protein supersaturation to cell dysfunction in ALS to provide further insight into the molecular origins of this disease.
- PNAS 114, E3935–E3943 (2017). doi: 10.1073/pnas.1613854114