New research from the United States is seeking to understand the neurological mechanisms behind Parkinson’s disease
Associate Professor of Biology Tamily Weissman’s research, supported by the National Institutes of Health (NIH), could shed light on new treatment pathways for Parkinson’s and other neurological disorders
Nearly one million people in the United States are living with Parkinson’s disease, making it the second-most common neurodegenerative disease after Alzheimer’s.
Current medical treatments for Parkinson’s are focused on helping people manage symptoms.
But the underlying mechanisms of the neurological disorder remain poorly understood.
Tamily Weissman, associate professor of biology and department chair, is working to change that.
Parkinson’s symptoms occur because of a drop in dopamine levels when certain brain cells die.
Scientists know that abnormal clumping of certain proteins inside key neurons is involved; however, the exact mechanisms are unclear.
Weissman said: “Something is causing these proteins to bind together and form aggregates, and we don’t yet understand what that mechanism does to cells or why the cells are dying.”
Similar protein aggregation is associated with other neurological disorders, including Alzheimer’s, amyotrophic lateral sclerosis (ALS), and Huntington’s disease.
A better understanding of these protein clumps, known as Lewy Bodies, could lead to breakthrough discoveries and open up new paths to treatment.
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Weissman’s work is focused on alpha-synuclein, the abnormally clumping protein found in the brains of Parkinson’s patients.
The National Institutes of Health (NIH) is funding her innovative approach, which examines how this protein behaves in zebrafish models.
She and her team are looking at the factors surrounding the phosphorylation at a protein site known as serine 129.
The site ‘gets tagged’ with a phosphate group, explained Weissman, who is also known for her work on a multicolour cell-labelling technique called Brainbow.
She said: “If you look at all of the aggregated alpha-synuclein, you’ll wonder, ‘Why has it all been tagged at that site? And in the same way? Nobody knows. It’s a total mystery.”
Weissman and her colleagues recently provided one key clue by confirming that phosphorylation at serine 129 cannot be the sole driver of the protein clumping.
She said: “Our question is; What else, in addition to the tag, needs to be in place for the clumping to occur?”
Weissman conducts her research with undergraduate students who work in the Weissman Lab.
Together, they conduct experiments that include injecting zebrafish embryos with alpha-synuclein DNA and manipulating the protein at different sites.
They mark it with fluorescence and, because the embryo is transparent, can then observe its behaviour using a confocal microscope.
This specialised microscope allows them to image the process in a high-resolution way, as well as to make observations over time.
The team is building collaborations with colleagues at Reed College and at Oregon Health & Science University, where researchers are also exploring the mechanisms behind alpha-synuclein.
Dr Vivek Unni’s lab is a direct collaborator on this research.
Weissman is excited about the work ahead and grateful for the support of the NIH and the Office of Sponsored Projects and Research Compliance (SPARC) at Lewis & Clark.
She said: “The SPARC office is one of the reasons why Lewis & Clark has done such a good job with securing and managing important research grants like this one.”
Image: This image shows multicolour motor neurons and their axons projecting from the zebrafish spinal cord. Credit: Zachary Tobias, in Weissman Lab at Lewis & Clark College.