Lay summary by Philippa Pease, reviewed by Dr Raquel Martins & a Parkinson’s Disease Lay Panel
Background
The brain has its own specialised immune system that helps protect it from infection and injury. A key component of this system is a type of immune cell called microglia, which constantly survey the brain’s environment and act as its first line of defence. In a healthy situation, when microglia detect damage or sense the presence of dying brain cells, they become activated and start clearing the environment by breaking down harmful material. However, in Parkinson’s disease, certain immune cells, including microglia, become chronically activated, meaning that they over-react and start breaking down material that is not harmful, leading to persistent inflammation and the loss of brain cells. This leads to gradual loss of brain cells that produce a chemical known as dopamine, which is crucial for controlling movement. Hence, the loss of these particular brain cells contributes to the development of typical motor symptoms of Parkinson’s disease such as tremor, stiffness and slow movement.
Scientists are therefore trying to understand what signals cause specific immune cells (microglia) to become harmful (chronically activated) rather than protective. This study particularly investigated whether certain proteins found on the surface of
Why is the study important?
Understanding why dopamine-producing brain cells gradually die in Parkinson’s disease is essential for developing treatments that can slow or stop disease progression. This is especially important because the current treatments only focus on managing symptoms of Parkinson’s disease rather than addressing the mechanisms that cause the disease. By studying a specific group of surface proteins that may drive harmful immune cell (microglial) activity, this study provides new insights into how the brain’s immune system might contribute to the disease. If microglia are mistakenly removing healthy dopamine-producing brain cells (by engulfing them and breaking them down), then targeting the immune cell surface proteins that drive this damaging response could help protect vulnerable brain cells and potentially lead to a new treatment for Parkinson’s disease.
What did the authors do and how did they do it?
To investigate how immune cells (microglia) might contribute to brain cell loss, the researchers studied 2 specific immune cell surface proteins called CD16 and CD32. The main function of these proteins is to detect debris or dying cells, influencing how immune cells (microglia) remove damaged/harmful material.
The authors used three different approaches as part of their research. Firstly, they examined post-mortem brain tissue from people with Parkinson’s disease to determine whether the presence of CD16 and CD32 were specifically increased in the region of the brain where dopamine-producing cells gradually die. Additionally, they tested whether mouse models of Parkinson’s disease had similar increases in the number of immune cell surface proteins when they triggered the loss of dopamine-producing brain cells using a toxin called MPTP. Finally, they performed laboratory experiments using immune cells (microglia) grown together in dishes with dopamine-like brain cells. This enabled them to study the impact of activating microglia (with certain molecules) on brain cells, specifically looking at death of dopamine brain cells.
What are the results?
The researchers found that the number of the two specific immune cell surface proteins (CD16 and CD32) were increased in the post-mortem tissue samples from people with Parkinson’s disease. The same was observed in the mice with Parkinson’s disease-like cell death. These results suggest that increased number of these immune cell surface proteins are associated with Parkinson’s disease. Additionally, when microglia grown in dishes were activated by inflammatory signals, they made direct contact with dopamine-producing brain cells and were able to engulf and remove these cells. Importantly, this process depended on the presence and activity of CD16 and CD32 on the immune cell surface, because when the researchers blocked these proteins or interfered with their signalling, microglia were much less able to eliminate dopamine-producing brain cells.
But how do we block these receptors? Commonly, by using antibodies. Antibodies are immune proteins that bind to very specific targets, effectively blocking their activity. In mouse models of Parkinson’s disease, treatment with antibodies against CD16 or CD32 prevented the loss of dopamine-producing brain cells. Overall, the findings suggest that these 2 immune cell surface proteins contribute to harmful immune cell activation and subsequent loss of brain cells, and therefore using antibodies to block these cell surface proteins could represent a promising treatment target.
It is important to keep in mind, however, that these models cannot fully replicate the complexity of the human brain. In reality, many other cell types and communication processes also influence Parkinson’s disease progression. Additional research is therefore needed to further understand these processes. Nonetheless, this research provides important insights into investigating how processes within the immune system could be targeted for potential new treatments. As such, future research should focus on determining if certain antibodies or drugs that block specific immune cell surface protein activity are safe and effective in humans and lead to promising treatments for Parkinson’s disease.
What do the findings mean going forward for people with the disease?
Currently, there are no treatments that slow down or prevent the loss of dopamine-producing cells in Parkinson’s disease. This study suggests that, in Parkinson’s disease, specific immune cells (microglia) contribute to the loss of dopamine-producing cells by mistaking them as foreign cells within the body and engulfing them – this harmful activity is triggered in the presence of the specific immune cell surface proteins discussed. Therefore, blocking these surface proteins could help protect vulnerable brain cells and slow the progression of Parkinson’s disease, opening new avenues for developing treatments.
This study can be found at https://doi.org/10.1038/s41531-025-01249-9
Paper Title:
Microglial low-affinity FcγR mediates the phagocytic elimination of dopaminergic neurons in Parkinson’s disease degeneration
Lead Authors
Casanova, P.V., & Barcia, C.
Publication details including date of publication
npj Parkinson’s Disease, Volume 12, Article 35. Published 16th January 2026.