Dr. Edward Griffin researches the relationship between neuroinflammation and Parkinson’s disease

Today we introduce you to Dr. Edward Griffin, a post-doctoral fellow at the University of Alabama at Birmingham. He is the recipient of a 2019-2020 APDA Post-doctoral fellowship and is currently studying the role of inflammation in the development of Parkinson’s disease (PD). We asked him questions about his work.

Q: What is the overarching goal of your research? What do you hope to find out?

A: As a PD researcher, I hope that by better understanding PD, we can find improved ways to prevent and treat the disease. PD is accompanied by the degeneration of nerve cells within the brain. I am exploring the role that the immune system and inflammation plays in this neurodegeneration.

It has been known for a while that inflammation is a key component in PD pathogenesis. However, the available tools and our incomplete understanding of neuronal immunology limited our knowledge of how the immune system influenced neurodegeneration. As a result, it was difficult to distinguish whether inflammation was a symptom or a cause of neurodegeneration in PD.

The brain has its own set of immune cells called microglia, that produce an inflammatory response to various stimuli. The inflammatory response sends signals to surrounding tissues to recruit assistance from additional specialized immune cells. One such cell is the T cell which typically circulates around the body, surveilling for possible enemies and relaying that information to other specialized units to coordinate a strategic immunologic attack. While these strategic attacks may be effective, they might result in collateral damage to unintended parts of the body, such as the brain.

When T cells are recruited to the brain for an immunologic attack, they tend to enter much more slowly than they enter other organs and may be more difficult to detect. Therefore, the contribution of T cells to neuroinflammation was largely overlooked until recently. Studies of brain trauma, stroke, and multiple sclerosis have revealed the significant negative effects that T cell mediated inflammation can have on neuronal tissue. We are working to understand specifically whether T cell mediated inflammation plays a role in neurodegeneration in PD. If this is the case, preventing T cell entry into the brain is an attractive therapeutic avenue, since drugs that block T cell entry into the brain are already approved by the Food and Drug Administration (FDA) in the treatment of multiple sclerosis.

Q: Could you describe how you perform your studies?

A: In PD, the protein alpha-synuclein (α-syn) misfolds, causing it to accumulate into small toxic aggregates. To create an animal model of PD, we isolated α-syn and induced it to form small toxic aggregates that were then injected into the brains of rats. Once in the brain, the small amount of misfolded α-syn causes molecules of the rat’s own α-syn molecules to misfold, thereby creating a cascade which leads to large toxic aggregates. This cascade results in pathology that is very similar to PD. For our experiments, we use special rats called nude rats that do not have T cells and compare them to normal rats that have T cells.

Over time, we collect the brains of these rats and examine them through various tests. In some cases, we separate the brain into individual cells and analyze them in a machine called a flow cytometer, to determine the amount of each distinct cell type in the specimen. With this technology, we can determine if different conditions cause changes in cell populations. We also slice the brain tissue to look at changes in anatomy and use antibodies to detect cell populations within those distinct areas of the brain. Using these techniques, we examine how the immune system responds to the toxic aggregates of α-syn.

Q: Can you tell us a little bit about what you have found out so far?

A: From what we have seen so far, the lack of T cells in nude rats results in decreased inflammation as compared to normal rats. We are currently analyzing neurodegeneration in rats with and without T cells that were injected with α-syn. If we see that neurodegeneration is decreased in the nude rats (that do not have T cells), we can move forward in the testing of FDA-approved drugs that block T cell entry into the brain as a potential therapeutic pathway.

Q: What fuels your passion for research?

A: I love being able to take a step back and look at how all the pieces of the puzzle fit together. I appreciate the chemistry of a biological system, much like how a mechanic or engineer might appreciate the machinery of an engine. It is satisfying to put together information from different models and techniques to understand biology. Unfortunately, much of disease is very complicated and can vary from patient to patient. My hope is that we can understand the biology of disease better so that our approaches can more strategically fight the disease.

Tips and Takeaways

• Every year, APDA funds brilliant researchers, like Dr. Edward Griffin, who are committed to unlocking the mysteries of PD.
• Griffin is studying the role of the T cell in the development of Parkinson’s disease.
• Blocking T cell entry into the brain may be a potential therapeutic pathway for PD.
• Research like this is only possible because of donations from dedicated people like you. If you would like to help APDA fund more of this critical work, please consider making a donation today.