The cause of neuronal death in Parkinson's disease is still unknown, but a new study proposes that neurons may be mistaken for foreign invaders and killed by the person's own immune system. "This is a new, and likely controversial, idea in Parkinson's disease; but if true, it could lead to new ways to prevent neuronal death in Parkinson's that resemble treatments for autoimmune diseases."
For decades, neurobiologists have thought that neurons are protected from attacks from the immune system, in part, because they do not display antigens on their cell surfaces. "That idea made sense because, except in rare circumstances, our brains cannot make new neurons to replenish ones killed by the immune system. But, unexpectedly, we found that some types of neurons can display antigens."
Cells display antigens with special proteins called MHCs. Using postmortem brain tissue donated to the Columbia Brain Bank by healthy donors [researchers] first noticed - to their surprise - that MHC-1 proteins were present in two types of neurons. These two types of neurons - one of which is dopamine neurons in a brain region called the substantia nigra - degenerate during Parkinson's disease.
[The researchers] conducted in vitro experiments with mouse neurons and human neurons created from embryonic stem cells. The studies showed that under certain circumstances - including conditions known to occur in Parkinson's - the neurons use MHC-1 to display antigens. Among the different types of neurons tested, the two types affected in Parkinson's were far more responsive than other neurons to signals that triggered antigen display. The researchers then confirmed that T cells recognized and attacked neurons displaying specific antigens.
"Right now, we've showed that certain neurons display antigens and that T cells can recognize these antigens and kill neurons, but we still need to determine whether this is actually happening in people. We need to show that there are certain T cells in Parkinson's patients that can attack their neurons. This idea may explain the final step. We don't know if preventing the death of neurons at this point will leave people with sick cells and no change in their symptoms, or not."