Researchers Find New Way to Stimulate Autophagy: It Could Treat Alzheimer’s or ALS

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Researchers at the Brown University have found a new way to stimulate cells that rebuild themselves from their old parts they recycle. The process is called autophagy and it could be stimulated to be part of the treatment in Alzheimer’s disease, ALS or other neurodegenerative conditions that appear in old age.

The study was published in the journal Cell Reports. The leader of the research is Louis Lapierre, an assistant professor of molecular biology, cell biology and biochemistry (Brown University). He and his team used human cells and looked at worms or flies that use autophagy to increase their lifespan:

“Autophagy dysfunction is present across a range of age-related diseases including neurodegeneration. We and others think that by learning how to influence this process pharmacologically, we might be able to affect the progression of these diseases. What we’ve shown here is a new and conserved entry point for stimulating autophagy.”

The Process – Working at a Cellular Level

In their study, the researchers gathered misfolded proteins and obsolete organelles from a cell into autophagosomes. The autophagosomes fused with an enzyme that contains organelle – known as lysosome. Lysosome breaks down macromolecules, converts them into components that the cell can reuse.

By manipulating a protein that regulated the activity of autophagy, Lapierre and his colleagues hoped that they could increase autophagy. They had to switch on the activity of autophagy by localizing the protein inside the nucleus of the cell. Researchers screened for the genes that enhances the protein (TFEB – the autophagy transcription factor) inside nuclei.

The team discovered that they had to reduce the expression of a protein (XPO1). This protein transports other proteins outside the nucleus. Lapierre explains what happened when they reduced the expression of XPO1:

“What we showed was that by blocking the escape of this transcription factor from the nucleus, we could not only influence autophagy but we could get an increase in lifespan as well.”

Successfully Stimulating Autophagy in Human Cells

Next, the team then focused on finding a drug that could have a similar effect. They used selective inhibitors of nuclear export (SINE). SINE had a similar effect in tests on a fruit fly. Lapierre said:

“Our data suggests that these compounds can alleviate some of the neurodegeneration in these flies.”

Finally, the last part of the study was testing XPO1 inhibition on human cells:

“Our study tells us that the regulation of the intracellular partitioning of TFEB is conserved from nematodes to humans and that SINE could stimulate autophagy in humans. SINE have been recently shown in clinical trials for cancer to be tolerated, so the potential for using SINE to treat other age-related diseases is there.”

Furthermore, Lapierre said that they will continue the research to see if drugs work in clinical trials in treating neurodegenerative diseases.

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Andre Blair s is the lead editor for Advocator.ca. He holds a B.A. in Psychology from the University of Toronto, and a Master of Science in Public Health (M.S.P.H.) from the School of Public Health, Department of Health Administration, at the University of North Carolina at Chapel Hill. Andre specializes in environmental health, but writes on a variety of issues.


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