In a recent scientific study at Brown University, researchers have discovered a new method of stimulating the body’s process of recycling old cell parts—called autophagy. This research could lend itself to helping to treat age related diseases such as Alzheimer’s disease. The study was published in the journal Cell Reports.
How Does Autophagy Work?
Autophagy is the process by which human cells recycle spare parts. The topic of autophagy has been very popular in recent years; it even took the 2016 Nobel Prize of Physiology and Medicine.
Autophagy involves the cell’s process of gathering misfolded proteins and outdated organelles (any structure within the cell that is enclosed within its own membrane and has a specific function) within the cell, into vesicles (a fluid filled sac within the cell). The vesicles involved in autophagy are called “autophagosomes.” Next the autophagosomes (after engulfing the old used up cell parts) fuse together with an enzyme-containing organelle called a lysosome. The lysosome then works to break down those large molecules in the vesicle and converts them into smaller components that the cell can re-use to build new structures.
The scientists were able to show that a new method of autophagy has increased the lifespans of flies and worms in lab experiments. Studies on human cells have backed up the researchers’ theory that this strategy could be very useful in the future treatment of Alzheimer’s disease, ALS, and other neurodegenerative conditions (diseases of the brain and nervous system that worsen with time) related to aging.
“Autophagy dysfunction is present across a range of age-related diseases, including neurodegeneration,” said Louis Lapierre, an assistant professor of molecular biology, cell biology and biochemistry at Brown University. Lapierre, who led the research project, added, “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 New Process of Stimulating Autophagy
As a person ages, the natural process of autophagy in the cell, does not function as well as it did when the organism (human) was younger. Lapierre and his team wanted to find out if they could increase the cell’s autophagy process, by manipulating a protein that turns the gene expression on and off. The specific protein is called transcription factor, and it is responsible for switching autophagic activity on. The researchers worked to discover which genes enhanced the level of autophagy transcription factor, which is scientifically referred to as TFFB—located in the cell’s nucleus. “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,” Lapierre explained.
The next phase of the study involved an attempt to find a drug that would replicate the effect the scientists had simulated. A drug that had previously been developed to treat cancer, called SINE was found to have a similar effect by increasing autophagy–which in turn, lengthened the lifespan in nematodes. The drug was used to test its effect on fruit flies—that had been genetically modified—in the lab. “Our data suggests that these compounds can alleviate some of the neurodegeneration in these flies,” Lapierre said.
The scientists then used human cells to see if the drug had a similar effect on humans as it did on the nematodes. “Our study tells us that SINE could stimulate autophagy in humans,” Lapierre said. “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.”
The study has given scientists optimism about the strategy for increasing autophagy to treat age related neurogenerative diseases in the future. Lapierre said he and his team will test the drug on “relevant models of neurogenerative diseases.”