Parkinson’s disease: autoimmunity jumps out of the horizon

Parkinson’s disease is a movement disorder caused by the loss of dopamine-producing cells in a part of the brain that deals with movement. Dopamine is an important messenger molecule that helps brain cells communicate with each other. The main symptoms of Parkinson’s disease include tremor, stiffness, slow motion and balance disorders. These can also be accompanied by depression and emotional changes. The disease manifests itself more often in people over the age of 60. and on average it is 1.5 times more likely to hit men than women. The symptoms are initially not very evident and progress at different rates in different people. In the end, it can become very difficult to walk, talk and live independently. All over the world, there are more than 10 million people living with Parkinson’s disease, about one million in the United States.

For the first time, scientists have found evidence that autoimmunity can play a role in Parkinson’s disease. They found that fragments of the protein that accumulates in the dopamine cells of the brains of people with Parkinson’s trigger an immune response that kills cells. The study – conducted by Columbia University Medical Center in New York City, New York and the La Jolla Institute for Allergy and Immunology in California – is published in the journal Nature. The results raise the possibility that the blocking of the discovered immune response may offer a new way to slow the progression of this brain wasting disorder. The exact causes of Parkinson’s disease are unknown, but an important hallmark is the accumulation of damaged alpha-synuclein protein in dopamine-producing cells.

The new study reveals evidence that two fragments of alpha-synuclein can activate T cells to initiate an attack by the immune system. The researchers tested blood samples from 67 patients with Parkinson’s disease and control samples from 36 healthy patients. They exposed blood samples to protein fragments in brain cells, including fragments of alpha-synuclein. The blood of the controls reacted slightly, but the T lymphocytes in the blood of patients with Parkinson’s had a strong reaction to the fragments defined by alpha-synuclein. Further investigations revealed that the immune response was linked to variants of a type of gene called major histocompatibility complex (MHC), which was found in many people with Parkinson’s disease.

MHC encodes proteins that collect protein fragments and “visualize” them on cell surfaces to inspect T cells. This is one of the pathways through which the immune system identifies threats. The finding suggests that some MHC variants – such as those associated with Parkinson’s disease – may cause T lymphocytes to mistakenly identify the alpha-synuclein fragments as pathogens and then trigger an autoimmune response that destroys the offending cells. More work will be needed to find out if the immune response caused by alpha-synuclein is the main cause of Parkinson’s disease, or if it simply contributes to the death of neurons and the progression of the disease after it has been activated.