Spermine vs Alzheimer’s & Parkinson’s!

Alzheimer’s and Parkinson’s are both neurodegenerative disorders that involve an accumulation of harmful proteins in the brain, including α-synuclein, β-amyloid (also called amyloid-β; it’s the exact same protein just written down differently), and tau protein*.

^{*…which just gets written like that instead of using a Greek letter τ, probably to avoid looking like the Greek letter τ that in mathematics denotes the ratio of the circumference to the radius of a circle (so in other words, 2π).}

Back to biology

Because of the association of those harmful proteins with the development and progression of neurodegenerative disorders, a lot of attention has been given to how to get rid of them.

In a health brain, the glymphatic system (a portmanteau of glial cells doing the job of the lymphatic system, but in the brain, where there is no lymph) does this adequately.

We’ve written about this previously, for example:

How To Clean Your Brain (Glymphatic Health Primer)

Take Care Of Your Lymphatic System To Beat Cognitive Decline ← still relevant because once the waste products have been removed from the brain, they still need to be removed further, or else they would just pile up right outside the brain, as though a city’s sanitation workers went on strike.

On which note, because the glymphatic system is strongly affected by gravity, the brain’s ability to remove toxins is dependent on the orientation of the head. This is critical for the clearance of α-synuclein and β-amyloid proteins, amongst others, and so this has a consequence that we’ve done a main feature about before:

• sleeping sideways is far better than sleeping on one’s back.
• sleeping on one’s right side is better than sleeping on one’s left side.

For more details on that, see:

Goodnight, Glymphatic System: How Your Sleep Position Changes Dementia Risk

Now, about spermine!

Firstly, what is it? Spermine is a rather small polyamine (protein made of more than one amino acid) that occurs naturally in most living cells of the body that are capable of mitosis.

Next, why is called that? Spermine was first identified in seminal fluid about 150 years ago, as it’s present in relatively high concentrations there. Aside from that, there is no particular connection with sperm, and as we say, it’s made throughout the body.

Finally, why is there a chef’s hat on the brain in the image next to this article’s title? For this one, you can blame the lead researcher, Dr. Jinghui Lui, who explained spermine’s anti-Alzheimer’s and anti-Parkinson’s powers in the following way:

❝Autophagy is more effective at handling larger protein clumps. And spermine is, so to speak, the binding agent that brings the strands together. There are only weakly attractive electrical forces between the molecules, and these organize them but do not firmly bind them together.

The spermine is like cheese that connects the long, thin noodles without gluing them together, making them easier to digest.

If we better understand the underlying processes, we can cook tastier and more digestible dishes, so to speak, because then we’ll know exactly which spices, in which amounts, make the sauce especially tasty.❞

Lexical note: Autophagy = literally, “eating oneself”; it’s the name given to the cellular process of “eating” old cells, either for recycling or waste disposal, or a combination of the above.

Now, maybe she got carried away in the last bit there about making the sauce especially tasty, but her point is that the presence of spermine causes the harmful proteins to clump in ways that make them easier for the body to eliminate.

You might be wondering how it does that, and to use slightly more scientific words than Dr. Lui’s cooking metaphor, spermine promotes biomolecular condensation—gently drawing protein fibers together through weak electrical interactions (like how static charge makes things cling together)—so that the cell’s waste-removal system can degrade them more efficiently.

You might next be wondering what level testing is at, and it’s currently at the level of our dear old friend C. elegans (a nematode, a kind of tiny worm, used a lot in biological research). Now, that may not sound inspiring of confidence, but C. elegans is used a lot in medical research of this kind because:

• Despite being very small and very simple, C. elegans shares many fundamental biological pathways with humans, including those governing aging, metabolism, stress responses, autophagy, and cell death. This makes it a great choice for first-line experiments in things pertaining to those areas of biology.
• Of particular relevance to this study, it has 302 neurons with a complete, published connectome—the only animal with a fully mapped neural wiring diagram—making it awesome for studying neurobiology and degeneration.
• And, as a bonus, the worm’s entire body is transparent, allowing real-time imaging of cellular processes, protein aggregation (yes, exactly of the kinds we’ve been talking about today), and more (we’ll be here all day if we list the things) without invasive procedures (that would create a confounding observer bias by killing the worm and thus halting the process, or at the very least injuring the worm and thus interfering with the process).

So that’s why Dr. Liu and her team used that.

Of course, C. elegans is only the first step, and future experiments will need to scale things up—probably mice next, then humans. A full step-by-step progression would go something like C. elegans → D. melanogaster (fruit fly) → mouse → non-human primate of some kind → human, but realistically, the only stages probably needed for this are nematode → mouse → human.

In summary: spermine’s protein-clustering effect can now accelerate the development of new treatments for neurodegenerative diseases.

You can read the (fascinating) paper in full, here: Spermine modulation of Alzheimer’s Tau and Parkinson’s α-synuclein: implications for biomolecular condensation and neurodegeneration

So… Should I eat sperm?

Well, don’t let us stop you if you feel so inclined, but no, there’s no medical reason to do so that we’re aware of, including the above.

We hit a similar issue issue with: Spermidine For Longevity ← note that this is spermidine, not spermine; similar name and similar etymology; different molecule!

…in which we noted:

Does that mean that consuming semen is good for longevity?

Aside from the health benefits of a healthy sex life… No, not really. Semen does contain spermidine as well as some important minerals, but you’d need to consume approximately 1 cup of semen to get the equivalent spermidine you’d get from 1 tbsp of edamame (young soy) beans.

Unless your lifestyle is rather more exciting than this writer’s, it’s a lot easier to get 1 tbsp of edamame beans than 1 cup of semen.

Learn more: Frontiers in Nutrition | Polyamines in Food

Enjoy!