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April 18, 2017
MILWAUKEE — New research by Marquette University biologists and mathematicians has found that newly formed prion amyloids are infectious, a discovery that provides insights into the early stages of neurodegenerative diseases.
Prions are the name given to the protein pathogen first discovered in the 1980s that is responsible for mad cow disease. This disease came to light a decade later when it was proposed that the infectious protein was responsible for variant Creutzfeldt-Jakob disease, the fatal human disease in the United Kingdom. Protein amyloids associated with other human diseases such as Alzheimer's and Parkinson's disease recently have been shown to have prion-like infectious qualities.
Until the Marquette study, scientists had not determined at which stage these prion amyloids became infectious. Using quickly reproducing yeast prions, scientists were able to closely study the early steps of prion amyloid formation in a living organism.
"Previous work has shown that mature amyloids, or amyloids that have around for a while, could be transmitted," said Dr. Anita Manogaran, assistant professor of biological sciences, the lead researcher for the study published recently in Scientific Reports . "It was unclear whether newly formed amyloids are pathogenic by themselves, or if amyloids need to mature or stick around for a while in order to be infectious. We isolated newly formed amyloids and were shocked that these misfolded proteins were infectious."
The primary author of the study was Jaya Sharma, a post-doctoral student in Manogaran's lab. In addition, researchers on the project were Stephen J. Merrill, a professor of mathematics, statistics and computer science; Emily Paulson, a graduate student in mathematics, statistics and computer science; and undergraduate biology students Brett T. Wisniewski and Joanna O. Obaoye.
Alzheimer's and Parkinson's disease are common in older patients, but the amyloid proteins that are associated with the disease are thought to buildup in the brain many years before symptoms appear. Little is known about what happens between the first appearance of amyloid and the onset of the disease.
Manogaran and her team used 4D live cell imaging to observe how the prion amyloids form in the cell in order to learn more about these early stages of amyloid formation.
"Our study shows that the formation of newly formed prion particles is more complex than previously thought," the researchers wrote in the study. "Prion particles can form through multiple pathways yet hold inherent infectivity."
The focus of the lab is to understand the cellular mechanisms that underlie amyloid formation associated with diseases such as Alzheimer's, Huntington's and Prion Disease, as well as ATTR amyloidosis. The lab studies the formation of prions, which are associated with transmissible spongiform encephalopathies, a family of neurological diseases that includes variant Creutzfeldt-Jakob disease in humans and "mad cow" disease in cattle.
The lab studies mathematical models in immunology by utilizing a variety of methods, including differential equations and stochastic techniques. The lab researches cardiac imaging, atrial fibrillation, thyroid autoimmune disease and cancer, malaria control and the mechanism of action of medicinal herbs.