Discovery Potentially Links How Neurodegenerative Diseases Spread Throughout the Brain

By Michael Hill

“I had different symptoms. They couldn’t figure out what it was,” said Lillian Marion.

Marion was diagnosed with Parkinson’s disease five years after she started showing symptoms. She lives at Jewish Family Home, home to a Parkinson’s center to help residents — and their families — through the aches and agony of the disease.

Marion says she’s living the reality that medical science seems handcuffed to improve the conditions of those afflicted with Parkinson’s and to get them beyond a plateau.

“Sinemet is a drug they give you for Parkinson’s, but it doesn’t seem to make much difference whether I take it or not,” Marion explained.

Ilija Melentijevic, a graduate student at Rutgers University, said, “I made this discovery as a sophomore.”

Seven years ago, when Melentijevic was just 18 years old, he discovered that a bright blob would form outside some cells in roundworms — which have the molecular form, function and genetics similar to humans.

“So, I was looking at how neurons were changing their shapes every day. Over the 15-day lifespan and during the process, I noticed the neurons would eject this large cell-size blob and the next day the blob would be gone. I was really curious about what this blob was doing. So, I started characterizing the function and started getting some time-lapse videos and eventually got a picture of what was going on. It was really exciting,” Melentijevic explained.

What was the department’s reaction?

“It took my professor a while to believe what I was saying, because I was a young student making a big claim,” said Melentijevic.

Distinguished professor of molecular biology and biochemistry, Monica Driscoll, put her full support behind the research. She says scientists have known how brain cells internally eliminate toxins, but Melentijevic found how they externally do it. The professor and the graduate student compare it to sorting and collecting trash and putting it on the curb, but if it stays there too long it could create some problems.

Melentijevic said, “We know that the neuron that ejects this material is healthier itself. So, we think it’s a way for the neuron to protect itself. We don’t know what the fate is in the surrounding tissue. So, potentially this could be something that might not happen sufficiently and the neurons end up dying from keeping the trash internally, or they could be sending it to the wrong cells who can’t handle it, or if there’s too much garbage at some point it might be toxic to the neighboring cells. We’re not sure of what the implications might be yet.”

The big questions in need of answers — what impact do those toxic proteins have on other cells? Are they making other cells sick? Are they making neurodegenerative diseases worse? And will researchers find the same results in cells of mice and humans?

“So, one of the big questions in the whole neurodegenerative disease family right now is, they know there are proteins that originate in one cell and they end up ceding through the whole brain. Sort of like in Alzheimer’s and Parkinson’s and even prion models. You see a localized toxic protein crisis and that ends up spreading through the brain. So, the question of how it goes from cell to cell to cell has really been pretty unclear right now and no one knows what pathways to investigate. We’ve shown that there is a way a cell could do this,” said Melentijevic.

The research at Rutgers could have monumental implications in the multi billion-dollar struggle against Alzheimer’s and Parkinson’s.

“If this mechanism is actually happening in humans, it could potentially open up a new pathway for pharmaceutical companies to target different parts of this mechanism to see. Maybe if you could turn it down or increase how much it happens. It might play a role in some of these diseases, but really we’re just speculating at this point for how much it might be involved,” said Melentijevic.

Researchers are in the early, early stages?

“Yeah. This is just the first to report that cells can do this at all,” he replied.

The research has gone through what Melentijevic describes as a grueling review process and will be published this week in the journal “Nature.” Melentijevic is the lead author. A first for the 25-year-old whose discovery might lead to breakthroughs in Parkinson’s and other neurodegenerative diseases. Perhaps too late for Marion, but hope for others.

Does she hope they find a cure?

Marion said, “That would be very nice.”