Researchers have found the first direct evidence that autoimmunity—in which the immune system attacks the body’s own tissues—plays a role in Parkinson’s disease, the neurodegenerative movement disorder. The findings raise the possibility that the death of neurons in Parkinson’s could be prevented by therapies that dampen the immune response.
The study was published in Nature.
Scientists once thought that neurons were protected from autoimmune attacks. However, in a 2014 study, the researchers demonstrated that dopamine neurons (those affected by Parkinson's disease) are vulnerable because they have proteins on the cell surface that help the immune system recognize foreign substances. As a result, they concluded, T cells had the potential to mistake neurons damaged by Parkinson's disease for foreign invaders.
The new study found that T cells can be tricked into thinking dopamine neurons are foreign by the buildup of damaged alpha-synuclein proteins, a key feature of Parkinson's disease.
In the study, the researchers exposed blood samples from 67 Parkinson's disease patients and 36 age-matched healthy controls to fragments of alpha-synuclein and other proteins found in neurons. They analyzed the samples to determine which, if any, of the protein fragments triggered an immune response. Little immune cell activity was seen in blood samples from the controls. In contrast, T cells in patients' blood samples, which had been apparently primed to recognize alpha-synuclein from past exposure, showed a strong response to the protein fragments. In particular, the immune response was associated with a common form of a gene found in the immune system, which may explain why many people with Parkinson's disease carry this gene variant.
The researchers hypothesize that autoimmunity in Parkinson's disease arises when neurons are no longer able to get rid of abnormal alpha-synuclein. The team is now analyzing these responses in additional patients, and are working to identify the molecular steps that lead to the autoimmune response in animal and cellular models.
Paper: “T cells of Parkinson's disease patients recognize alpha-synuclein peptides”
Reprinted from materials provided by Columbia University Medical Center.