In the search for clues to Parkinson’s disease (PD), researchers have uncovered evidence that shows autoimmunity may be part of the answer. Autoimmunity occurs when the immune system attacks the body’s own tissues, and new research has discovered that in people with PD, the immune system is activated by fragments of alpha-synuclein, the protein that clumps to form Lewy bodies in people with PD.1,2
Alpha-synuclein and Parkinson’s
Alpha-synuclein is a protein that is found in nerve cells (neurons). In people with PD, the protein accumulates into Lewy bodies and is believed to contribute to the damage of the neurons. Damage to the neurons in the part of the brain called the substantia nigra pars compacta produce dopamine, a neurotransmitter (chemical messenger) that is involved in communicating the signals for smooth, purposeful movement. When the dopamine-producing neurons are damaged, the motor symptoms of PD become apparent.3,4
T-cells identify alpha-synuclein fragments as foreign
In the recent study, researchers from Columbia University Medical Center and the La Jolla Institute for Allergy and Immunology collected blood samples from 67 people with PD and 36 age-matched healthy control subjects. The blood was then exposed to fragments of alpha-synuclein and other proteins that are found in neurons.
In the healthy controls, there was little immune activity detected, but in the blood samples from people with PD, there was a significant response. Researchers believe that the T-cells (specialized white blood cells that recognize and destroy cells that are infected or defective) in people with PD have been primed to recognize alpha-synuclein from past exposure – the exposure being the presence of Lewy bodies in the brain. The immune response seen in the study subjects with PD was associated with a common gene variant that is known to affect the immune system, a gene variant that is common in people with PD.
Researchers hypothesize that autoimmunity in people with PD may develop when the neurons are no longer able to rid themselves of the abnormal accumulations of alpha-synuclein. In normal, healthy cells, old or damaged proteins are broken down and eliminated, but this process is not functioning properly in PD. When alpha-synuclein begins to form clumps, the immune system may mistakenly see it as a pathogen that needs to be attacked.1,2
Potential new treatment strategies
This new finding provides additional knowledge and understanding of the disease processes that are present in PD and opens the door for using immunotherapies, drugs that suppress the abnormal immune response seen in autoimmune disorders. Additional research is needed to understand the molecular steps that occur in PD and the immune response, but researchers are hopeful that an immunotherapy strategy could help to prevent or lessen worsening symptoms in people with PD.1,2
Science Daily. Accessed online on 7/24/17 at https://www.sciencedaily.com/releases/2017/06/170621132904.htm
Sulzer D, et al. T cells of Parkinson's disease patients recognize alpha-synuclein peptides. Nature. 2017;546:656-661. doi: 10.1038/nature22815
National Parkinson Foundation. Accessed online on 7/24/17 at http://www.parkinson.org/understanding-parkinsons/what-is-parkinsons
Parkinson’s Disease Foundation. Accessed online on 7/24/17 at http://www.pdf.org/en/about_pd.