As with most biological molecules, proteins are being made, used, and disposed of all the time in neurones.
Tight regulation of this process means that if a protein is damaged in any way it is disposed of rapidly. A characteristic trait of motor neurones in MND is that proteins accumulate into deposits. These deposits are large ‘junk piles' that the cell has not been able to eliminate. Many forms of MND are associated with deposits of the protein made from instructions of the TDP-43 gene, while some familial MND cases are associated with deposits of protein made from the mutant SOD1 gene. Researchers in Japan have shown that mutations in the FUS gene mean that the protein it encodes accumulates and is found in deposits in motor neurones but also in non-neuronal brain cells called astrocytes. This suggests that protein accumulation is a common characteristic of all forms of MND. This knowledge may one day lead to identifying a therapeutic target.
Source: International MND research update - June 2010, Dr Justin Yerbury for MNDRIA