Is Parkinson's an autoimmune disease?

April 17, 2014
Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease. Credit: Wikipedia

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, similar to the way autoimmune diseases like type I diabetes, celiac disease, 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 in Parkinson's that resemble treatments for ," said the study's senior author, David Sulzer, PhD, professor of in the departments of psychiatry, neurology, and pharmacology 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 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 exempt from T-cell attacks.

"That idea made sense because, except in rare circumstances, our brains cannot make new neurons to replenish 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 donors, 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 neurons in a brain region called the substantia nigra—degenerate 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 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.

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.

"Right now, we've showed that certain neurons display antigens and that T cells can recognize these antigens and kill neurons," Dr. Sulzer says, "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."

If the does kill neurons in Parkinson's disease, Dr. Sulzer cautions that it is not the only thing going awry in the disease. "This idea may explain the final step," he says. "We don't know if preventing the death of at this point will leave people with sick cells and no change in their symptoms, or not."

Explore further: Stem cell-derived dopaminergic neurons rescue motor defects in Parkinsonian monkeys

More information: "MHC-1 expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration." Nature Communications, 2014.

Related Stories

Stem cell-derived dopaminergic neurons rescue motor defects in Parkinsonian monkeys

December 3, 2012
Parkinson's disease is a degenerative disorder of the central nervous system that is characterized by tremors, rigidity, slowness of movement, and difficulty walking. It is caused by loss of the neurons that produce the neurotransmitter ...

Research shows that a human protein may trigger the Parkinson's disease

April 9, 2014
A research led by the Research Institute Vall d'Hebron (VHIR), in which the University of Valencia participated, has shown that pathological forms of the α-synuclein protein present in deceased patients with Parkinson's ...

New explanation for cognitive problems of Parkinson's patients

November 28, 2012
The hallmark of Parkinson's Disease is the uncertain gait and movement caused by the destructions of neurons producing the neurotransmitter dopamine.

Generating dopamine via cell therapy for Parkinson's disease

July 2, 2012
In Parkinson's disease, the loss of dopamine-producing cells in the midbrain causes well-characterized motor symptoms. Though embryonic stem cells could potentially be used to replace dopaminergic (DA) neurons in Parkinson's ...

Recommended for you

Singing may be good medicine for Parkinson's patients

August 11, 2017
(HealthDay)—Singing? To benefit people with Parkinson's disease? It just may help, a researcher says.

Tracing the path of Parkinson's disease proteins

August 4, 2017
As neurodegenerative disorders such as Parkinson's and Alzheimer's disease progress, misfolded proteins clump together in neurons, recruiting normal proteins in the cell to also misfold and aggregate. Cells in which this ...

Diabetes drug shows potential as disease-modifying therapy for Parkinson's disease

August 3, 2017
A drug commonly used to treat diabetes may have disease-modifying potential to treat Parkinson's disease, a new UCL-led study suggests, paving the way for further research to define its efficacy and safety.

Two new studies offer insights into gastrointestinal dysfunction in Parkinson's patients

July 31, 2017
Constipation is one of the most common non-motor related complaints affecting Parkinson's disease (PD) patients. Two important studies from the same research group published in the Journal of Parkinson's Disease expand the ...

New drug may treat and limit progression of Parkinson's disease

July 31, 2017
Researchers at Binghamton University have developed a new drug that may limit the progression of Parkinson's disease while providing better symptom relief to potentially hundreds of thousands of people with the disease.

A new insight into Parkinson's disease protein

July 28, 2017
Abnormal clumps of certain proteins in the brain are a prominent feature of Parkinson's and other neurodegenerative diseases, but the role those same proteins might play in the normal brain has been unknown.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.