Millions of people worldwide are diagnosed and treated for Parkinson’s disease (PD). Unfortunately, in the U.S., there are about 1 million people with PD and 90,000 new cases each year. While the risk of PD is increased with age, there are cases of young-onset PD (YOPD). Additionally, biological men tend to be more at risk than biological women. The progressive neurodegenerative disorder can affect movement, balance, and other motile functions. As a result, many symptoms are related to movement including, tremors, slow reflexes, muscle rigidity, postural instability, walking difficulties, and others. As the disease progresses, speech can also become impaired, and an individual may experience fatigue, difficulty sleeping, and a decline in cognitive ability.
While the exact cause of PD is unknown, many scientists have discovered how it impairs body movement. In patients with PD, neurons or nerve cells in the brain can’t produce enough of a chemical, called dopamine, which is responsible for helping the brain communicate with the musculoskeletal system to move. Researchers speculate the disease could be hereditary and passed on by genetic variants in a human’s DNA. Other possible risk factors include exposure to chemicals and toxins within the environment.
Many scientists are working on understanding and learning more about PD. Recently, a paper in the Journal of Clinical Investigation (JCI), by Dr. Cecilia S. Lindestam Arlehamn and others, demonstrated sex-based differences in the immune response to PD. Arlehamn is an Assistant Professor at the La Jolla Institute for Immunology. Her research focuses on immune cell-mediated immunity and how our body’s recognize foreign pathogens. She also specializes in autoimmunity and allergic disease to understand how immune cells best adapt and work to maintain a robust immune response.
Arlehamn and her team set out to understand what drives PD. They discovered a protein that serves as a potential target to treat PD and helps explain why men are more susceptible to the neurodegenerative disease. The team found that immune cells target a protein, known as PINK1, on nerve cells. Interestingly, this protein helps regulate cell function and wasn’t thought to have any direct impact on the pathology of PD. Scientists found that immune cells sometimes recognize this protein as foreign and attack the nerve cells that cause inflammation and cell death.
This discovery helps explain why biological men might be more prevalent to PD. In the same study, researchers noticed that there were significantly more immune cells that targeted PINK1 in biological men compared to biological women. Researchers speculate that the immune response to PINK1 expressing cells helps drive PD onset and progression. The increased expression of PINK1 could also serve to detect PD at earlier stages of development.
Arlehamn and her team suggest that other proteins could also help accurately predict PD as well as become targets for treatment. The discovery of PINK1 triggering an immune response that promotes PD is a groundbreaking discovery and helps explain sex-based prevalence. As a result, this work has the potential to not only provide a marker to diagnose PD earlier, but also serves as a target for immunotherapy that would improve patient survival and quality of life.
Paper, JCI, Cecilia S. Lindestam Arlehamn, La Jolla Institute for Immunology