Researchers have discovered that the small molecule spermine has the potential to prevent the buildup of toxic proteins in the brain that are characteristic of diseases such as Alzheimer’s and Parkinson’s, acting a bit like melting cheese on spaghetti.
We’ve known about spermine for over 150 years: its daily work is involved in the body’s metabolism, converting food into energy, and keeping all critical biological functions running.
Here, researchers led by a team from the Paul Scherrer Institute (PSI) in Switzerland found that giving worms with Alzheimer’s and Parkinson’s disease-like symptoms an additional injection of spermine improved health in old age, with cells less likely to lose power and wear out.
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Careful analysis of the cells in test tubes revealed what was happening: Spermine prompted the proteins tau and alpha-synuclein (which typically show up poorly in Alzheimer’s and Parkinson’s diseases) to clump together to form liquid-like droplets.
In turn, this makes these toxic proteins more easily cleared by the body’s waste recycling system, called autophagy, thus maintaining normal cellular function. There’s even a cooking analogy to describe what’s going on.
“Spermine acts like cheese, tying long, thin pieces of pasta together instead of sticking them together, making them easier to digest,” said Jinghui Luo, a biophysicist at PSI.
When spermine was given to the worms (bottom row), it reduced the levels of protein aggregation (highlights). (Sun et al., Nat. comminicate.2025)
Tau and alpha-synuclein are so-called amyloid proteins, and when these proteins malfunction, they form hard, sticky aggregates that damage brain cells in neurodegenerative diseases.
It’s not entirely clear whether these clumps are a cause or consequence of Alzheimer’s and Parkinson’s disease, but they are certainly involved.
Concentrates also produce some kind of clumps, but they are softer and easier to move. This makes them easier to remove through the body’s cleanup system, while also preventing the proteins from forming solid plaques – which can then act like crusty food stuck to the bottom of a pan and be more difficult to remove.
“Autophagy is more efficient at processing larger protein clumps,” Luo said. “Spermine is the glue that holds the strands together, so to speak.”
“There are only weak attractions between the molecules that organize them but don’t hold them firmly together.”
What’s more, the researchers showed that spermine only interferes with tau and alpha-synuclein at too high a concentration and is more likely to misfold under stress, resulting in toxic clumps.
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Obviously, there’s a long way to go from experiments in test tubes and worms to seeing all of this working in the brains of people with Alzheimer’s or Parkinson’s disease, but these early signs are good. Extra spermine may help the brain clear problematic proteins more efficiently.
Spermine was chosen for this study because it has previously been shown to prevent damaging processes in the brain.
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Following these results, researchers hope that spermine and similar molecules could be used to treat a variety of diseases, including cancer—almost like a special sauce mixed together to eliminate toxic processes.
“If we better understand the underlying processes, we can cook dishes that are more palatable and easier to digest, because then we know exactly which spices and amounts make the sauce particularly delicious,” Luo said.
The study was published in nature communications.