TDP-43 accumulation is a hallmark of sporadic MND.
TDP-43 is normally predominantly located in the cell compartment that houses the DNA, the nucleus. However, during MND it is found outside the nucleus where it accumulates. The reason that this occurs is not known. One possibility is that the mechanism that transports TDP-43 back into the nucleus is faulty. Just like a key would get us back into a locked room, so too proteins need specific "keys" or "passwords" in order to pass through the gate of the nucleus. Researchers from London have explored the factors that regulate the transport of TDP-43 and found that the key that TDP-43 uses to get back into the nucleus (called CAS) is deficient in MND patients. The researchers propose that this knowledge could be used to target TDP-43 nuclear transport as a possible treatment.
Source: International MND research update - June 2010, Dr Justin Yerbury for MNDRIA