My PD Story

Highlighting the Connections between Parkinson's, Immune Responses and the Gut

It is becoming clear that gut and brain health are intrinsically connected. This connection is referred to as the “gut-brain axis.” Parkinson’s disease (PD) is no exception. Several studies highlight how gastrointestinal issues, such as constipation, commonly show up before movement symptoms when it comes to PD — often by years or decades. While the pathways linking gut health specifically to PD progression are still unknown, Juliet Taylor, PhD, and recipient of a Parkinson’s Foundation Impact Award, believes that an important element involved is type-I interferon (IFN) signaling, a part of the body’s immune response toolkit.

From her lab at the University of Melbourne in Parkville, Australia, Dr. Taylor seeks to understand how early IFN disturbances in the gut may lead to later PD development, and whether affecting such signaling can slow or prevent overall disease progression.

Meet IFN. Even those well-versed in Parkinson’s may not be familiar with type-I interferon (IFN) receptors. IFN’s help the body fight infection. Parkinson’s Foundation researcher, Juliet Taylor, is investigating whether IFN issues in the gut may lead to later PD development, and whether affecting signaling can slow or prevent overall disease progression.

IFN proteins are secreted by white blood cells, often in response to infections to stimulate immune responses. The ability of IFNs to quickly drive the body to fight back against invaders has its risks, however, since prolonged or improper IFN signaling can cause major stress and damage to cells and organs. IFN regulation has been shown to be critical in the gut, where the intestinal walls constantly encounter and prevent infection by microbes.

Dr. Taylor and her team have recently discovered that lab-created gut organoids — three-dimensional collections of gut cells that can be used to mimic live tissue — injected with PD-associated alpha-synuclein clusters (the protein associated with PD) show increased IFN production. To better understand this immune reaction to alpha-synuclein in the gut, Dr. Taylor will create variations of gut organoids with and without IFN signaling receptors and see how they react to alpha-synuclein exposure, helping to determine which gut cell types are most important in the response.

Next, Dr. Taylor will examine how alpha-synuclein injected into the gastric (gut) walls of young and old mice affects overall gastrointestinal health as well as how it may spread to the brain to cause PD-like neurodegeneration and movement symptoms. She will also use genetically engineered mice that lack the IFN-receptors to further explore how that pathway is associated with PD progression along the gut-brain axis.

Speaking on how the Parkinson’s Foundation award will support her lab’s research goals, Dr. Taylor said, “While the majority of research has focused on the brain pathology and associated motor symptoms in PD, there is increasing interest in the non-central nervous system effects of the disease, specifically the gut dysfunction experienced in many patients’ years earlier… The studies supported by this funding will develop a model within our laboratory that will potentially identify a novel modulator of the gut-brain axis in PD and therefore pave the way for future studies.”

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