My PD Story

2025 Impact Award 

Highlighting Alpha-synuclein Clumps in PD with Small Molecule Trackers 

Tracking Parkinson’s disease (PD) progression is challenging. Doctors currently rely mostly on how a person’s symptoms change over time. Because those symptoms vary from person to person and can fluctuate from day to day, this approach can make it difficult to evaluate whether treatments are truly helping. 

For other brain diseases like Alzheimer’s, scientists have developed small molecules that can attach to disease-related protein clumps and make them visible on brain scans such as PET (positron emission tomography). These imaging tools allow researchers and clinicians to see where harmful proteins are building up in the brain, providing a clearer, more objective way to track disease progression and test therapies. 

Sarah Shahmoradian, PhD, recipient of a Parkinson’s Foundation Impact Award, is exploring whether a similar biomarker tag could work for Parkinson’s. Working with collaborators at Massachusetts General Hospital, a Parkinson’s Foundation Center of Excellence, Dr. Shahmoradian is studying a specially designed small molecule that appears to bind strongly and selectively to misfolded alpha-synuclein clumps—the abnormal protein deposits that are a hallmark of Parkinson’s disease. 

“We aim to provide the first atomic-resolution view of how a promising small-molecule PET tracer binds to alpha-synuclein fibrils in human Parkinson’s brain,” says Dr. Shahmoradian. 

Inside the brain, misfolded alpha-synuclein proteins can form dense clusters that disrupt how nerve cells work. Evidence suggests these toxic protein forms may even spread from one neuron to another, contributing to the gradual worsening of symptoms in PD. A molecule that can label these alpha-synuclein clumps could allow researchers and physicians to visualize Parkinson’s pathology directly in the living brain—an advance that could transform diagnosis, treatment monitoring and research. 

From her lab at the University of Texas Southwestern Medical Center in Dallas, Dr. Shahmoradian will use high-resolution imaging methods — developed through her earlier Parkinson's Foundation-supported research— to see precisely how this new molecule attaches to alpha-synuclein fibrils. Understanding this interaction at the molecular level will help scientists fine-tune the tracer for future clinical imaging. 

The next step is to adapt the molecule so it glows under the microscope. By applying it to neurons grown in the lab that model Parkinson’s disease, or to slices of PD brain tissue, Dr. Shahmoradian and her team hope to track where alpha-synuclein clumps appear and how they move inside cells. If successful, this work will demonstrate that the molecule can serve as a powerful diagnostic and research tool for Parkinson’s. 

“This award gives me the opportunity to pursue a line of research I see as essential for advancing how we detect and monitor Parkinson’s disease,” said Dr. Shahmoradian. “This research will help accelerate the development of clinically useful biomarkers for early diagnosis and therapeutic monitoring in PD.” 

2022 Stanley Fahn Junior Faculty Award  

Learning About Early-Stage Accumulation of Alpha-Synuclein in the Parkinson’s Brain

Sarah Shahmoradian, PhD, of the University of Texas Southwestern Medical Center, received a Parkinson’s Foundation Stanley Fahn Junior Faculty Award to study early-stage build-up of a protein called alpha-synuclein in the brain.

“Results from these studies will fundamentally advance our understanding of how Parkinson’s disease develops,” Dr. Shahmoradian said. “They could thereby inform on novel therapeutic strategies.”

Parkinson’s disease (PD) is characterized by the misfolding of the alpha-synuclein protein into an abnormal shape. These shapes clump together to form sticky deposits in the brain that disrupt the brain’s ability to produce dopamine — and are connected to cognitive decline and dementia. This build-up appears to occur early in the disease.

About Alpha-Synuclein: When it comes to Parkinson’s disease, the protein called alpha-synuclein plays a key role. This protein begins to form sticky clumps in neurons (cells in the brain) in people with PD. Over time, the clumping kills healthy neurons and impairs the brain’s ability to produce dopamine, leading to Parkinson’s symptoms and ultimately a diagnosis.

Prior research has largely focused on the late stages of alpha-synuclein deposits. However, much is still not known about the critical early events that cause a single abnormal alpha-synuclein molecule to recruit and transform additional molecules to becoming toxic. This leads to build-up and spreading to other brain cells.

Ongoing research is focused on where alpha-synuclein first begins to accumulate in the brain. Previous studies have used high-resolution imaging to analyze alpha-synuclein that is either chemically extracted from the human brain or artificially produced. However, researchers still do not know if the molecular structure of the toxic form of alpha-synuclein can be found in a natural state within brain cells.

Dr. Shahmoradian will apply state-of-the-art, high-resolution imaging techniques to uncover the molecular structure of alpha-synuclein within the brain cells, and to study how alpha-synuclein contributes to the disease process in Parkinson’s. This research will define where and how alpha-synuclein buildup first occurs within human brain cells.

Of her Parkinson’s Foundation award, she said, “Being granted this generous support from the Parkinson’s Foundation cements my commitment to continue research in Parkinson's disease. Through receiving this award from an organization intimately linked to those affected by PD, I feel a heightened sense of personal responsibility and urgency in executing my research.”