University Scientists Make Breakthrough in Alzheimer’s Research

University of Michigan researcher Ayyalusamy Ramamoorthy, a professor of chemistry and biophysics, made a breakthrough in his research on age-related diseases, and he and his team have received a grant from National Institutes of Health to conduct further studies.

The team has discovered a protein that appears to be significantly linked to the cell death that causes memory loss in Alzheimer’s patients. They are working on discovering how this protein and the cell’s membrane interact to cause this cell death.

“We are investigating how this membrane plays a role in protein aggregation, that would lead to different types of aggregated species,” Ramamoorthy said. “Before they go into needle-like structures, you see that plaque. Needle-like structures are not toxic, but the intermediate structures are the most toxic species. So my research has been investigating this intermediate species. We would like to know their high-resolution structure, at what times they can form, how they execute cell membrane toxicity, so that we can develop compounds to incubate this kind of toxicity. And they may become potential drugs to treat disease, or they would aid in the design of compounds to treat these diseases.”

Ramamoorthy also discovered these proteins can punch holes in the membrane, which is the second mechanism they have found to cause this cell death and memory loss.

“It is like a tornado,” Ramamoorthy described. “When a tornado comes, the buildings get destroyed, and when the protein aggregates like a tornado, it just rips out the whole cell membrane.”

While the research team is focused particularly on Alzheimer’s due to the grant they received, they have also discovered proteins that could tell more about Type 2 diabetes, AIDS and bone diseases.

Mi Hee Lim, an associate professor of chemistry at the Ulsan National Institute of Science and Technology in Korea, wrote in an email stating she thought the diversity of backgrounds in this team had a big effect on making this discovery.

“This research field absolutely needs multidisciplinary approaches in order to identify such a big question,” Lim wrote. “Working with this team has been very fruitful to verify challenging questions in Alzheimer’s disease.”

Magdalena Ivanova, an assistant professor of neurology and biophysics and a member of Ramamoorthy’s research team, said while she is more of a biochemist, her expertise complements that of Ramamoorthy. Ivanova has no personal connection to Alzheimer’s, but she believes Alzheimer’s and other diseases caused by aging should be things of public concern by all.

“Most aging people are developing Alzheimer’s disease, more or less,” Ivanova said. “So the longer you live, your chances increase significantly. So with the increased lifespan, everybody starts to worry about these things.”

Ramamoorthy does not have a personal connection to Alzheimer’s either, but his father did suffer from Type 2 diabetes, which served as a personal motivation for him.

“I’m very interested in brain-related diseases,” Ramamoorthy said. “We are living in an electronic world, but nature has chosen the brain to control everything. And the brain is so complicated, so contributing towards understanding of these molecule events that disrupt the brain is exciting.”

Ramamoorthy was excited about these new developments, but acknowledged there is still a great deal of work to be done in understanding the brain.

“I wish a day would come where we could clean up our brain the same way you clean up your body,” Ramamoorthy said. “We could go where the proteins are aggregated and put the brain back.”
Ramamoorthy laughed, and said hope is “like a science-fiction.”

Ivanova shared a similar sentiment, saying there is still a long way to go in terms of creating a drug to combat Alzheimer’s.

“Drugs are not so simple,” Ivanova said. “I think this is a big step forward to finding a cure, or knowing what to target and what to modify, so in that respect I’m optimistic that this could lead to a drug, or at least finding a good target to develop a drug.”

An article titled, “University scientists make breakthrough in Alzheimer’s research” originally appeared in The Michigan Daily.

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