Researchers here provide evidence for Parkinson’s disease to have a significant autoimmune component, adding to other factors known to contribute to the death of dopamine generating neurons that is characteristic of this disease. It is certainly the case that the growing dysfunction of the immune system in later life includes a variety of autoimmune aspects, and that those aspects are still poorly mapped. It is reasonable to expect that researchers will continue to uncover ways in which immune system failures contribute to well-known age-related conditions in the years ahead. The disovery here is particularly interesting, as it links autoimmunity to the buildup of metabolic waste and consequent failure of mechanisms of maintenance that is observed in aging. This is a target for the SENS rejuvenation research program, and therapies built on this approach should prove broadly beneficial, precisely because they will halt and turn back many chains of consequences akin to that reported by the researchers here.
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 idea that a malfunctioning immune system contributes to Parkinson’s dates back almost 100 years. But until now, no one has been able to connect the dots. Our findings show that two fragments of alpha-synuclein, a protein that accumulates in the brain cells of people with Parkinson’s, can activate the T cells involved in autoimmune attacks. It remains to be seen whether the immune response to alpha-synuclein is an initial cause of Parkinson’s or if it contributes to neuronal death and worsening symptoms after the onset of the disease. These findings, however, could provide a much-needed diagnostic test for Parkinson’s disease and could help us to identify individuals at risk or in the early stages of the disease.”
Scientists once thought that neurons were protected from autoimmune attacks. However, in a 2014 study, 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 most cases of Parkinson’s, dopamine neurons become filled with structures called Lewy bodies, which are primarily composed of a misfolded form of alpha-synuclein.”
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.
Researchers hypothesizes that autoimmunity in Parkinson’s disease arises when neurons are no longer able to get rid of abnormal alpha-synuclein. “Young, healthy cells break down and recycle old or damaged proteins, but that recycling process declines with age and with certain diseases, including Parkinson’s. If abnormal alpha-synuclein begins to accumulate, and the immune system hasn’t seen it before, the protein could be mistaken as a pathogen that needs to be attacked.”