Researchers at the Paul Scherrer Institute PSI have clarified how spermine – a small molecule that regulates many processes in the body’s cells – can guard against diseases such as Alzheimer’s and Parkinson’s: it renders certain proteins harmless by acting a bit like cheese on noodles, making them clump together. This discovery could help combat such diseases. The study has now been published in the journal Nature Communications.
Our life expectancy keeps rising – and as it does, age-related illnesses, including neurodegenerative diseases such as Alzheimer’s and Parkinson’s, become increasingly common. These diseases are caused by accumulations in the brain of harmful protein structures consisting of incorrectly folded amyloid proteins. Their shape is reminiscent of fibres or spaghetti. To date, there is no effective therapy to prevent or eliminate such accumulations.
Yet a naturally occurring molecule in the body called spermine offers hope. In experiments, researchers led by study leader Jinghui Luo, in the Center for Life Sciences at the Paul Scherrer Institute PSI, have discovered that this substance is capable of extending the life span of small nematode worms, improving their mobility in old age, and strengthening the powerhouses of their cells – the mitochondria. Specifically, the researchers observed how spermine helps the body’s immune system eliminate nerve-damaging accumulations of amyloid proteins.
The new findings could serve as a basis for developing novel therapies for such diseases.
A central mediator of cellular processes
Spermine is a vital substance for the organism. It belongs to the so-called polyamines, which are relatively small organic molecules. Spermine, first discovered more than 150 years ago, is named after the seminal fluid, as it is found in particularly high concentrations there. But it also occurs in many other cells of the body – especially those that are active and capable of dividing.
Spermine promotes cell mobility and activity and controls numerous processes. Above all, it interacts with the nucleic acids of the genome, regulating the expression of genes and their conversion into proteins. This ensures that cells can properly grow and divide and ultimately die. Spermine is also central to an important cellular process called biomolecular condensation: In this process, certain macromolecules, such as proteins and nucleic acids, segregate and collect within the cell in a droplet-like form, so that important reactions can take place there.
In connection with neurodegenerative diseases such as Alzheimer’s or Parkinson’s, there has previously been evidence that spermine can protect nerve cells and alleviate age-related memory loss. Lacking until now, however, has been a more precise understanding of how spermine intervenes in nerve-damaging processes – understanding that might make it possible to derive medical benefits from it.
Assisting cellular waste removal
Jinghui Luo’s group has now investigated this in more detail. In addition to optical microscopy, the researchers also used the SAXS scattering technique at PSI’s Swiss Light Source SLS to shed light on the molecular dynamics of these processes. The investigations were conducted both in a glass capillary (in vitro) and in a living organism (in vivo). The nematode C. elegans served as a model organism.
Read more on the PSI website
Image: Jinghui Luo is a researcher at the Center for Life Sciences at the Paul Scherrer Institute PSI. He studies accumulations of so-called amyloid proteins, which lead to nerve damage in the brain. His research aims to help mitigate neurodegenerative diseases such as Alzheimer’s and Parkinson’s in the long term.
Credit: © Paul Scherrer Institute PSI/Markus Fischer
