The PTEN-induced kinase 1 (PINK1) protein is not typically harmful. In fact, it plays an important role by regulating cellular energy use in the brain. However, new research has shown that in some cases of Parkinson’s disease, the immune system mistakenly identifies PINK1 as an enemy and attacks brain cells that express the protein.
A team at the La Jolla Institute for Immunology in California found that damage linked to PINK1 caused by T cells is significantly more common and aggressive in the brains of men than in women.
“The differences in T-cell responses based on sex were very, very striking. This immune response may explain why we observe sex differences in Parkinson’s disease,” noted immunologist Alessandro Sette, a co-author of the study.
Parkinson’s disease is a chronic, progressive brain disorder. Patients experience motor and speech disturbances, constant muscle stiffness, resting tremors, and mental health issues.
How Was the Study Conducted?
Using blood samples from patients with Parkinson’s disease, the team examined how T cells in the blood responded to various proteins previously linked to the disease. The researchers found that PINK1 triggered the strongest T-cell response, as reported by Science Alert.
In male patients with Parkinson’s disease, the researchers observed a sixfold increase in T cells targeting brain cells marked by PINK1 compared with healthy brains. In female patients with Parkinson’s disease, there was only a 0.7-fold increase.
Some participants in the study had previously noted a similar phenomenon with T cells and the protein alpha-synuclein. However, those responses were not uniform across all Parkinson’s patients, prompting the search for more antigens—substances that trigger immune reactions.
As researchers learn more about how the disease begins and progresses, this work opens new avenues for exploring treatments.
“Now that we understand why these cells attack the brain, we could develop treatments that block these T-cells,” said immunologist Cecilia Lindestam Arlehamn, another co-author of the study.
Detecting PINK1-sensitive T cells in blood samples may help diagnose Parkinson’s disease earlier.
The study was published in the Journal of Clinical Investigation.
