A new study funded in part by the Parkinson’s Foundation shows how the loss of brain neurons in Parkinson’s disease (PD) could, in part, result from an attack by a person’s own immune system. Furthermore, the researchers link this attack to alpha-synuclein – the protein that forms toxic clumps in the brain cells of people with PD. The results appear in the June 21 online edition of Nature.
In autoimmune diseases like type 1 diabetes and multiple sclerosis, the immune system attacks and kills specific cells in the body that are mistakenly labeled or “flagged” as foreign. The cells actually have a molecular flag, indicating that they are foreign. The “flag” is called an antigen, and the flagpole an MHC.
At one point, scientists ruled out the possibility of PD being an autoimmune disease because neurons did not seem to have MHC or the “flagpoles.” But David Sulzer, Ph.D., and colleagues at the Parkinson’s Foundation Research Center at Columbia University Medical Center, proved this wrong three years ago, demonstrating for the first time that human brain cells have MHC. Since then, genetic studies and studies in rodents have added to the evidence that PD may be linked to an autoimmune reaction, perhaps driven by the protein alpha-synuclein.For the new study, Sulzer’s team investigated this relationship in people with PD. They collected blood samples from 67 people with PD and 36 healthy individuals of similar age. They analyzed the DNA of the participants to see if they carried any PD risk factors associated with the immune system. With a range of other methods, the scientists broke the alpha-synuclein protein into small peptide pieces and tested whether these pieces could act as an antigen, or “flag,” to attract immune cells found in the blood taken from the study participants.
- About a third of people with PD had immune-related DNA risk factors previously linked to PD, compared to 15 percent of healthy individuals.
- Scientists identified two specific pieces of the alpha-synuclein protein that caused the immune cells to respond.
- Immune system cells from people with PD more often recognized specific peptides, or pieces, of alpha-synuclein.
What Does it Mean?
Previously, researchers have demonstrated many ways in which the protein alpha-synuclein, in an abnormal form, can wreak havoc in the brain cells lost in PD. But it has not been clear how this leads to cell death in PD.
This study finds that abnormal alpha-synuclein can activate an attack on brain cells by the body’s own immune-system cells and potentially trigger an immune response in the brain. More specifically, the researchers suggest that PD may, in part, be an autoimmune disorder. Understanding more about how the immune system is involved in PD may lead to new approaches to preventing the brain cell death that underlies PD.
Sulzer D, Alcalay RN, Garretti F, et al. (2017). T Cells from Patients with Parkinson’s Disease Recognize α-Synuclein Peptides. Nature doi:10.1038/nature22815