Study clarifies how spermine can protect against Alzheimer's and Parkinson's

Study clarifies how spermine can protect against Alzheimer's and Parkinson's

Researchers at the Paul Scherrer Institute PSI have explained how spermine - a small molecule that regulates many processes in the body's cells - can prevent diseases such as Alzheimer's and Parkinson's: It renders certain proteins harmless by acting a bit like cheese on pasta and causing them to clump together. This discovery could help combat such diseases. The study has now been published in the scientific journalNature communication.

Our life expectancy continues to increase - and with it the frequency of age-related diseases, including neurodegenerative diseases such as Alzheimer's and Parkinson's. These diseases are caused by accumulations of harmful protein structures in the brain made up of misfolded amyloid proteins. Their shape is reminiscent of fibers or spaghetti. To date, there is no effective therapy to prevent or eliminate such accumulations.

But a molecule called spermine that occurs naturally in the body offers hope. Researchers led by study leader Jinghui Luo from the Center for Life Sciences at the Paul Scherrer Institute PSI have discovered in experiments that this substance is able to extend the lifespan of small nematode worms, improve their mobility in old age and strengthen the power plants of their cells - the mitochondria. Specifically, the researchers observed how spermine supports the body's immune system in eliminating nerve-damaging accumulations of amyloid proteins.

The new findings could serve as a basis for the development of novel therapies for such diseases.

A central mediator of cellular processes

Sperm is a vital substance for the organism. It is one of the so-called polyamines, which are relatively small organic molecules. Sperm, first discovered more than 150 years ago, is named after seminal fluid because it occurs there in particularly high concentrations. But it is also found in many other cells in the body - especially those that are active and capable of division.

Spermine promotes cell mobility and activity and controls numerous processes. It interacts primarily with the nucleic acids of the genome and thus regulates the expression of genes and their conversion into proteins. This ensures that cells can grow and divide properly and eventually die. Sperm also play a central role in an important cellular process called biomolecular condensation: In this process, certain macromolecules such as proteins and nucleic acids separate and collect in droplet-like form within the cell, allowing important reactions to occur 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. So far, however, there has been a lack of a more precise understanding of how spermine intervenes in nerve-damaging processes - knowledge that could derive medical benefit from it.

Support in eliminating cellular waste

Jinghui Luo's group has now investigated this in more detail. In addition to optical microscopy, the researchers also used SAXS scattering technology at PSI's Synchrotron Light Source Switzerland SLS to elucidate the molecular dynamics of these processes. The examinations were carried out in a glass capillary (in vitro) and in a living organism (in vivo). The nematode C. elegans served as a model organism.

It turned out that spermine uses biomolecular condensation to ensure that the harmful proteins accumulate and, to a certain extent, clump together. This enables a process called autophagy that occurs routinely in our cells: damaged or unnecessary proteins are wrapped in small membrane vesicles and safely broken down using enzymes - practically a natural recycling process.

Autophagy is more effective at treating larger clumps of proteins. And spermine is, so to speak, the binding agent that holds the strands together. There are only weakly attractive electrical forces between the molecules, which organize them but do not firmly connect them to one another.”

Jinghui Luo, director of studies

The whole thing, says Luo, can also be imagined as a plate of spaghetti. “The spermine is like cheese, binding the long, thin noodles together without sticking them together, making them easier to digest.”

Looking for: the right combination of ingredients

Sperm also has an impact on other diseases, including cancer. Here, too, there is a need for research to clarify the mechanisms of action - then spermine-based therapeutic approaches would be conceivable. In addition to spermine, there are many other polyamines that fulfill important functions in the organism and are therefore of medical interest. Therefore, research in this area has great potential. “If we understand the underlying processes better,” says Luo, “we can cook tastier and more digestible dishes, so to speak, because then we know exactly which spices and in what quantities make the sauce particularly delicious.”

Artificial intelligence is also used in this search because it can calculate promising combinations of “sauce ingredients” much more quickly based on all available data. Luo also points out that time-resolved scattering measurement techniques and high-resolution imaging, which can image such processes in real time and down to the subcellular level, are also important for this and subsequent studies. Apart from PSI, such methods are only available at a few other synchrotron facilities worldwide.

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