How a small worm may help the fight against Alzheimer’s

During ageing, proteins in the human body tend to aggregate. At a certain point, protein aggregation becomes toxic, overloads the cell, and thus prevents it from maintaining normal function. Damage can occur, particularly in neurons, and may result in neurodegenerative diseases like Alzheimer’s, Parkinson’s or Huntington’s disease. By studying model organisms like C. elegans, scientists have begun to uncover the mechanisms underlying neurodegeneration, and thus define possible targets for both therapy and prevention of those diseases. “Although we cannot measure dementia in worms“, explains Martin Denzel of the MPI for Biology of Ageing, “we can observe toxic proteins that we also know from human diseases like Alzheimer’s by measuring effects on neuromuscular function. This gives us insight into how Alzheimer actually progresses on the molecular level“.

A broad-spectrum effect that could alleviate various neurodegenerative diseases

Now, the scientists Martin Denzel, Nadia Storm, and MPI Director Adam Antebi have discovered that a substance called N-acetylglucosamine apparently stimulates the body’s own defense mechanism against such toxicity. This metabolite occurs naturally in the organism. If it is additionally fed to the worm, “we can achieve very dramatic benefits“, says Nadia Storm. „It is a broad-spectrum effect that alleviates protein toxicity in Alzheimer’s, Parkinson’s and Huntington’s disease models in the worm, and it even extends their life span“. This molecule apparently plays a crucial role in quality control mechanisms that keep the body healthy. It helps the organism to clear toxic levels of protein aggregation, both preventing aggregates from forming and, in some cases, clearing already existing ones. As a result, onset of paralysis is delayed in models of neurodegeneration. – How exactly the molecule achieves this effect is yet to be uncovered. “And we still don’t know whether it also works in higher animals and humans“, says Antebi. “But as we also have these metabolites in our cells, this gives good reason to suspect that similar mechanisms might work in humans.”
A related compound, glucosamine, is used to treat joint problems, but its effectiveness is unclear. Whether N-acetylglucosamine can be used to treat dementias or other age-related diseases in humans is an open question.

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