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Insights from Cheesy Noodles Inform Neurodegenerative Disease Research

A common molecule in sperm cells shows promise for treating Alzheimer’s and Parkinson’s

A cheesy bowl of mac and cheese. Credit: Rimma Bondarenko / Shutterstock.

You know how your noodles clump up when you add cheese to them? It’s yummy in a gooey way, with the individual noodles losing their separation. According to a new study, cheesifying your noodles provides a useful model for combating Alzheimer’s and Parkinson’s diseases, which, albeit, have much more dire consequences than the texture of your lunch.

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In neurodegenerative diseases, which affect about 8 million people in the United States, toxic buildups of proteins cause devastating symptoms of memory loss and motor disruptions. Misfolding of proteins found in all animals makes the proteins prone to accumulating into tangles and messing up the functioning of the nervous system. 

But researchers at the Paul Scherrer Institute in Switzerland have found a promising treatment in a molecule called “spermine.” Spermine (named for its abundance in sperm cells) occurs naturally in many of our cells, playing roles in regulating cell metabolism and gene activity. 

Spermine had already gained attention for its effects on preserving and restoring memory in fruit flies and nematode worms. Fruit flies sometimes forget how to climb as they age, but in one 2015 study, feeding spermine-like molecules to the insects sustained their climbing abilities and lifespans. But while the effects of spermine had been observed, the mechanism of its action remained unknown.

Read more: “What You Don’t Know About Sperm

By experimenting with nematode worms in the lab that were modified to contain high levels of the human brain protein bits prone to misfolding, the team of scientists discovered that spermine causes misfolded proteins to condense into semi-liquid blobs, like boluses of cheesy noodles.

The blobs are recognized and therefore purged in the body’s natural, cellular recycling process—autophagy—that packages waste products into membranes and degrades them with enzymes. “Autophagy is more effective at handling larger protein clumps,” explained lead study author Jinghui Luo in a statement. “And spermine is, so to speak, the binding agent that brings the strands together.”

Because spermine has also been studied for its ability to treat other diseases, such as cancer, and because there are other spermine-like molecules that might be useful, the researchers are using artificial intelligence to ferret them out. Luo likens the search to finding “ingredients for the sauce” on the noodles. 

In the nematode worms used as disease models, the spermine treatment recovered normal cell functions, restored movements, and prolonged their lifespans. The challenge now is to see whether spermine and related molecules can “cheesify” misfolded proteins in human brains to facilitate their removal.

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Lead image: Rimma Bondarenko / Shutterstock

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