University of Michigan scientists have identified a novel and potential drug that speeds up trash removal from the lysosome.
The finding suggests a new way to treat rare inherited metabolic disorders such as Niemann-Pick disease and mucolipidosis Type IV, as well as more common neurodegenerative diseases like Alzheimer's and Parkinson's, said Haoxing Xu, who led a U-M team that reported its findings March 13 in the online, multidisciplinary journal Nature Communications
"The implications are far-reaching," said Xu, an assistant professor of molecular, cellular and developmental biology. "We have introduced a novel concept—a potential drug to increase clearance of cellular waste—that could have a big impact on medicine."
Xu cautioned, however, that the studies are in the early, basic-research stage. Any drug that might result from the research is years away.
In cells, as in cities, disposing of garbage and recycling anything that can be reused is an essential service. In both city and cell, health problems can arise when the process breaks down.
Inside the trillions of cells that make up the human body, the job of chopping up and shipping worn-out cellular components falls to the lysosomes. The lysosomes—there are several hundred of them in each cell—use a variety of digestive enzymes to disassemble used-up proteins, fatty materials called lipids, and discarded chunks of cell membrane, among other things.
Once these materials are reduced to basic biological building blocks, the cargo is shipped out of the lysosome to be reassembled elsewhere into new cellular components.
The steady flow of the materials through and out of the lysosome, called vesicular trafficking, is essential for the health of the cell and the entire organism. If trafficking slows or stops, the result is a kind of lysosomal constipation that can cause or contribute to a variety of diseases, including a group of inherited metabolic disorders called lipid storage diseases. Niemann-Pick is one of them.
In previous studies, Xu and his colleagues showed that proper functioning of the lysosome depends, in part, on the timely flow of calcium ions through tiny, pore-like gateways in the lysosome's surface membrane called calcium channels.
If the calcium channels get blocked, trafficking throughout the lysosome is disrupted and loads of cargo accumulate to unhealthy levels, swelling the lysosome to several times its normal size.