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Researchers "shocked" by finding that ALS-diseased neurons show incredible resistance if given glucose



Increased glucose, transformed into energy, could help people with ALS improve mobility and longer life, according to a new study.

Physicians have long known that people with ALS experience changes in metabolism that often lead to rapid weight loss in a relentless cycle called hypermetabolism, according to a research team at the University of Arizona.

People with ALS spend more energy while resting, compared to those without the disease while at the same time often struggling to effectively use glucose, a precision component that the body needs for more energy. Experts do not know exactly what is happening in the patient's cells to cause this dysfunction or how to alleviate it.

"This project was a way of presenting these details," said principal researcher Ernesto Manzo, who described the results, published on the Internet eLife, as "truly shocking".

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The study found that when neurons with ALS get more glucose, they convert that source of energy into energy. With this energy, they can survive and work better. Increasing the delivery of glucose to cells, therefore, may be one of the ways to meet the abnormally high energy needs of ALS patients.

"These neurons found relief by degrading glucose and getting more cellular energy," said Manzo.

ALS is almost always a progressive disease, which ultimately seizes the ability of patients to walk, speak, and even breathe. The average life expectancy of ALS patients since the diagnosis is two to five years.

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Previous studies on ALS patients metabolism focused primarily on what is happening at the level of the entire body, not at the cellular level, explained Daniel Zarnescu, a professor of molecular and cell biology and a senior author of the study.

Researchers have been watching the cerebral haunches of fruit flies with ALS under a microscope. The picture is a nervous ribbon, populated with green motor neurons, which express human glucose transporter. The neurotransmitter release regions are shown in red color, while the muscles are shown in blue. (Courtesy of Laboratory Zarnescu)

"The fact that we discovered the compensation mechanism surprised me," Zarnescu said. These desperate, degenerative neurons have shown incredible resistance. This is an example of how stunning cells are faced with stress.

The novelty in the findings is partly due to the fact that metabolism in ALS patients remained poorly understood, Zarnescu said.

"It's hard to study, partly because of the limited access to the nervous system," she said.

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Since scientists can not release neurons from the brain without causing irrefutable harm to the patient, researchers have used fruit flies as a model.

"Fruit flies can teach us much about human illnesses," said Manzo.

In the lab, he and Zarnescu used powerful microscopes to observe motor neurons of fruit flies in their livers, paying particular attention to what happened while they gave more glucose.

They found that when they increase the amount of glucose, motor neurons live longer and more efficiently. When the researchers separated glucose from the neurons, the fowl larvae moved slower.

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Their findings were in line with a pilot-clinical study that showed high-carbohydrate nutrition as one of the possible interventions for ALS patients with a fast metabolic disorder.

"Our data is essentially explaining why this approach could work," Zarnescu said. "My goal is to convince clinicians to conduct a larger clinical trial to test this idea."

Printed from the University of Arizona

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