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Eyes Wide Open

Nora Caberoy discovered that her research on proteins in the eye might someday help us fight Alzheimer’s.

Research  |  Sep 21, 2016  |  By Shane Bevell
Nora Caberoy looks through microscopw slide

Cell and molecular biologist Nora Caberoy. (Josh Hawkins/UNLV Photo Services)

Editor's Note: 

This piece is a sneak preview of a larger feature coming out in the 2016 issue of Innovation magazine, which promotes UNLV research. To celebrate this and the many other research, scholarly, and creative activities taking place at UNLV, join us for Research Week 2016 from Oct. 3-7. All events are free, but some require an RSVP. Visit our Research Week webpage for the most current list of events.


Cell and molecular biologist Nora Caberoy never thought that a protein she worked with years ago could potentially lead to new discoveries in the fight against Alzheimer’s disease. But that’s exactly what the protein, called “tubby” because it is encoded by the TUB gene, may offer scientists.

It all started in 2007 while Caberoy, now an assistant professor in UNLV’s School of Life Sciences, was working as a postdoctoral fellow at the Bascom Palmer Eye Institute in Miami. While occupied on a project related to macular degeneration — a retinal condition that causes a loss in central vision — she identified a tubby protein that is involved in the clearance of photoreceptor debris in the eye.

Photoreceptors are cells responsible for reception and processing of light and sending the signal to the brain. When old bits of cellular debris accumulate around the ends of photoreceptors, these need to be removed.

Specialized cells make this happen, but they need proteins to guide the process. This is where tubby comes in. Tubby proteins bind onto cellular debris while inviting another type of cell, phagocytes, to begin clearing it. Tubby serves, in other words, as a bridge between the cells that need to be consumed and those that are supposed to eat them.

So, what does all this have to do with Alzheimer’s disease? Patients with Alzheimer’s have an accumulation of amyloid beta, a protein that aggregates in the brain. Caberoy says that, for reasons that are not entirely clear, the amyloid beta deposits of those with Alzheimer’s squeeze in between the brain cells, eventually killing them.

“We all produce amyloid beta, but in healthy individuals, the production of amyloid beta is somehow equal to the degradation,” she says. “In those with Alzheimer’s, the balance is not equal.”

According to Caberoy, the body maintains this balance in part thanks to the work of debris- and pathogen-eating microglial cells that, in addition to gobbling up diseased cells, also have a taste for excess amyloid beta. But many scientists suspect that this microglial assault may have a serious side effect: an increase in inflammation that may hasten the disease’s progress and the subsequent death of brain cells.

Caberoy noted from her research on photoreceptors that the tubby protein assisted in the removal of damaged cells in the eye without inflammation. Could they perhaps be repurposed for use in the brain?

“We know that the active receptor in the eye also is present in the brain, but for some reason, it is not the preferred receptor,” she said. “We also know that the molecules that bridge that amyloid beta is not binding directly to the receptor.”

In an attempt to make that happen, Caberoy is working to create a new type of molecular “bridge,” one that could link amyloid beta to a less inflammatory protein that might neutralize it.

In the lab, her research team undertook screenings to discover proteins that could bind to amyloid beta. They were able to identify several. Caberoy then “optimized” these proteins by mutational analysis until she found one that could bind to the most toxic form of amyloid beta.

“I fused the amyloid beta binding protein to the part of tubby that recognizes the silent receptor,” she said. “Through testing, we were able show that chimeric protein, which is created through the joining of two or more separate proteins, was able to bind to both the receptor and the amyloid beta. We also found that this process could reduce the production of inflammatory factors.”

Over the next few months, Caberoy’s research team will test this process on mice with Alzheimer’s. She says they will first inject the affected mice with the chimeric protein, then see if it results in a reduction in the level of amyloid beta in the brain with the production of inflammatory factors in the blood.

If successful, this process will bolster the patent application Caberoy has been submitted for this method of clearing amyloid beta.

Additionally, if the results are positive, the approach could eventually be used to develop therapies for human patients, although she cautions that there are still questions as to whether such treatment would need to be deployed before the disease develops or if it might help individuals already affected.

Regardless, she says, there is much to be hopeful about.

“There could be clinical applications where we would produce proteins that could be injected into an individual,” she says. “You can imagine someone that has a family history of Alzheimer’s disease taking a pill or getting an injection before the disease develops.”