Two University of Florida Health researchers have made a discovery that could provide a novel way to target the brain deterioration associated with amyloid plaque build-up in Alzheimer’s disease. Diego Rincon-Limas, Ph.D., an assistant professor in the department of neurology and a member of the UF Genetics Institute, along with Todd Golde, Ph.D., director of the Center for Translational Research in Neurodegenerative Disease and a professor in the department of neuroscience, led a team of UF scientists who published a paper about the study in a recent issue of the Proceedings of the National Academy of Sciences.
Amyloid plaques are thought to be a key contributor to Alzheimer’s symptoms. They form when a protein called amyloid-β, which is normally made in the brain, accumulates outside neurons in the brain. There is a strong link between amyloid plaque build-up and the eventual development of Alzheimer’s symptoms. However, a lot remains unknown about how amyloid plaques damage the brain.
“We accumulate amyloid-β in our brain, and sometime later we’re in either widespread or regional brain organ failure,” Golde said. “What happened in between?”
The research team manipulated a protein that occurs naturally within cells, called Hsp70, that recognizes amyloid proteins as they are misforming and forces them to form normally. The researchers found that this protein, when deliberately introduced outside the cells where amyloid-β accumulates, is able to bind abnormal forms of amyloid-β and block toxicity.
As Alzheimer’s disease is often not diagnosed until well into the progression of the illness, Rincon-Limas said it would be a significant discovery just to find something that would slow further deterioration. However, Golde suggested merely halting the progression of plaque build-up might not be enough — methods for blocking toxicity are also necessary.
“Initiation of the pathology could be so far removed from what’s happening by the time you’re in brain organ failure — we don’t know,” Golde said.
The study was conducted in the eyes of fruit flies. Eyes are full of photoreceptor neurons, making it easy to see under a microscope whether the eye has developed abnormalities as a result of amyloid toxicity. Afterward, the research team moved on to conducting tests within fruit fly brains to confirm their findings.
The discovery has potential applications in diseases with similar pathologies, such as Type 2 diabetes. Another cause for optimism is that the protein Hsp70 has many substrates, meaning it can bind a variety of amyloids as they misform.
Rincon-Limas said the next goal is to determine whether secreted Hsp70 can stop or delay amyloid-β toxicity after the initial pathology has been triggered. This would signal that it might be possible to not only prevent toxicity, but also halt it after it has begun.
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R21NS081356. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
This article was originally published by UF Health
Ellison Langford, UFGI