NEW YORK—Parkinson’s disease, like Alzheimer’s disease, is one of the leading neurodegenerative issues being targeted by the biopharmaceutical and life sciences industries today. It is the result of the death of neurons responsible for producing dopamine, which the Parkinson’s Disease Foundation describes as “A chemical messenger that regulates movement by assisting in the effective communication (transmission) of electrochemical signals in the brain from one nerve cell (neuron) to another.” When the dopamine deficiency increases, it results in the loss of autonomous movement control Parkinson’s disease is known for.
Given the role dopamine plays in the disease, most work has focused on trying to increase dopamine production. But a new study has suggested that attention should be turned onto the immune system, as Parkinson’s disease might be an autoimmune condition.
In a standard immune system, the body’s white blood cells recognize antigens—which can take the form of bacteria, viruses or toxins—on infected cells and produces T cells to destroy them. In autoimmune diseases, such as type 1 diabetes, multiple sclerosis, rheumatoid arthritis and lupus, the immune system mistakes healthy cells for antigens, which results in damage to healthy tissue.
Parkinson’s disease has not previously been considered in the category of autoimmune diseases because it the prevailing belief is that since neurons do not display antigens on their cell surfaces, they are safe from immune system attacks.
Cells display antigens with proteins known as MHCs. A team led by Dr. David Sulzer, professor of neurobiology in the departments of psychiatry, neurology and pharmacology at Columbia University College of Physicians & Surgeons, worked with postmortem brain tissue donated by healthy donors to the Columbia Brain Bank and found MHC-1 proteins in two types of neurons. Both types of neurons degenerate in patients with Parkinson’s disease, and one type is dopamine neurons located in the substantia nigra region of the brain. Dopamine deficiency is credited as one of the leading issues of Parkinson’s disease.
The next step in their work was to determine if living neurons use MHC-1 to display antigens, or for another purpose. Sulzer and Dr. Carolina Cebrián, his postdoc, experimented in vitro with mouse and human neurons created from embryonic stem cells. Those experiments demonstrated that in certain cases, including conditions known to present in Parkinson’s disease, neurons use MHC-1 to display antigens. Additionally, the two types of neurons affected in Parkinson’s disease were found to be significantly more responsive to signals that trigger antigen display than other neurons. The team was also able to confirm that T cells recognized and attacked neurons that presented with specific antigens.
While the in-vitro experiments certainly support the theory that Parkinson’s disease maybe be an autoimmune issue, Sulzer cautioned that “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.”
Like with cancer, however, this is likely only one of several factors responsible for the disease, according to Sulzer, who added that “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.”
“This is a new, and likely controversial, idea in Parkinson’s disease,” said Sulzer, “but if true, it could lead to new ways to prevent neuronal death in Parkinson’s that resemble treatments for autoimmune diseases.”
The paper, titled “MHC-1 expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration,” appeared in Nature Communications on April 16.