“Inclusion bodies – those clumps of protein that are found in the brain cells of Alzheimer’s patients – are, sadly, a product of aging,” says Dr. Maya Schuldiner. “They can form naturally in practically all cells, but when these cells get old, the mechanism for clearing them away starts to fail.”
That is not great news for those of us who are already seeing signs of incipient dementia every time we forget a name or misplace our keys. But of course there is good news too. Schuldiner has discovered a “detergent” that cells make to wash away those nasty protein clumps. And she believes that, in the future, this detergent could provide the basis of drugs to treat neurodegenerative diseases, among them Alzheimer’s and Parkinson’s.
We put the word “detergent” in quote marks, but the truth is that the basic chemistry is pretty much the same as that of laundry soap: The two-part molecules have a fatty, water-repelling end and a water-loving end. The fatty end can attach to molecules of grease or protein; the water-loving ends latch on to the nearest water molecules to whisk the “dirt” away. In scientific terms, the proteins in the inclusion body become soluble.
Schuldiner and her team realized this detergent was being produced when they saw lipid droplets – “little lard balls,” in Schuldiner’s words – tethered to the inclusion bodies they were investigating in yeast cells. These little lard balls turn out to be a bit more complex than they look. They produce a special kind of fat that is similar to a sterol (related to cholesterol) – when and only when there is an inclusion body in the cell. This sterol is what forms the detergent.
She says that she and her team were amazed to find evidence of detergents inside a cell. Since detergent molecules are basically indiscriminate in their actions – capable of clearing away all sorts of proteins and fats – the cell would need to produce them carefully and deliberately in place. Hence the physical tethering.
Her lab mostly works with yeast cells, which have, says Schuldiner, “the same inclusion body issues as human cells. They contain a protein that is nearly identical to the human one for tethering the lipid droplets. And, like the human ones, they suck at the removal process once they get old.” The group did repeat their experiments on human cells in lab dishes, finding similar results to their yeast cell studies. And Schuldiner points out that other studies have noted the lipid droplets around inclusions in the nerve cells of Alzheimer’s patients, but mostly ignored the deceptive little “lard balls.”
What gives her hope for treatment is that the detergent production is really “basic chemistry.” Clearly any potential drugs based on her group’s findings are, for now, in the speculation stage, but we can all hope for rapid advances in this area.
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