The cause of neuronal death in Parkinson's disease is still unknown, but a new study proposes that neurons may be mistaken for foreign invaders¹ and killed by the person's own immune system, similar to the way autoimmune diseases like type I diabetes², celiac disease（乳糜泻）, and multiple sclerosis attack the body's cells. The study was published April 16, 2014, in Nature Communications. "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," said the study's senior author, David Sulzer, PhD, professor of neurobiology in the departments of psychiatry³, neurology, and pharmacology（药理学） at Columbia University College of Physicians & Surgeons.

 

The new hypothesis about Parkinson's emerges from other findings in the study that overturn a deep-seated assumption about neurons and the immune system.

 

For decades, neurobiologists have thought that neurons are protected from attacks from the immune system, in part, because they do not display antigens（抗原） on their cell surfaces. Most cells, if infected by virus or bacteria, will display bits of the microbe (antigens) on their outer surface. When the immune system recognizes the foreign antigens, T cells attack and kill the cells. Because scientists thought that neurons did not display antigens, they also thought that the neurons were exempt⁴ from T-cell attacks.

 

"That idea made sense because, except in rare circumstances, our brains cannot make new neurons to replenish⁵（补充） ones killed by the immune system," Dr. Sulzer says. "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 donors⁶, Dr. Sulzer and his postdoc Carolina Cebrián, PhD, 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（多巴胺） neurons in a brain region called the substantia nigra -- degenerate⁷ during Parkinson's disease.

 

To see if living neurons use MHC-1 to display antigens (and not for some other purpose), Drs. Sulzer and Cebrián conducted in vitro experiments with mouse neurons and human neurons created from embryonic⁸ 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 affected⁹ 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.

 

The results raise the possibility that Parkinson's is partly an autoimmune disease, Dr. Sulzer says, but more research is needed to confirm the idea.

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