Prion protein overview
No website da Infekta encontramos um artigo com o título acima. É um texto em inglês, com data de publicação de maio de 2024. E que não resisto a partilhar…
A proteína priónica em nome próprio.
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A. M.
I am not alive. I am not dead.
You have called us prions.
Pronounced “pree-ons”.
I am going to talk about a special prion, that is…me.
I am a prion because I am protein material and I am infectious.
Infectious not in the sense that I cause those disgusting diseases like bacteria, fungi, parasites or viruses do. No. Infectious because I can propagate within you and harm you. Sooo sooorry…And I can pass from one of you…to another of you.
I do these things so well that you once thought I was a virus…
Aargh.
In fact, I am
you.
You see, you are made of many molecules, including many proteins.
One of them you have called prion protein. Or PrP, in your so beloved abbreviations. Pleased to meet you.
There is one of my variants that some of your cells, mainly cells of your central nervous system, have on their surface. A protein that you have called cellular prion protein, or PrPC.
They are not the most exciting names you have chosen for me, but you are forgiven.
I am encoded by a gene that was named PRNP (prion protein gene). PRNP is highly conserved across many mammals. In you humans, it is located on chromosome 20.
As PrPC, I sometimes get conformational changes.
Why? I confess. I am too vain.
There is one that gives me the most superb look…This variant of mine you have called scrapie prion protein, or PrPSc.
Later in this letter, you will understand why scrapie.
You can get an idea of me as PrPc and as PrPSc from images you have put on this Internet of yours. You can see one of them by clicking here.
As PrPC (cellular prion protein), I am attached to the cell plasma membrane and I have more of an α-helical structure and less of a β-sheet structure.
As PrPSc (scrapie prion protein), I stay in both the intracellular and extracellular spaces, and I have more of a β-sheet structure and less of an α-helical structure.
And when I am in this new PrPSc version of mine, you call me aberrant!
Thank you!
I am so fantastic as PrPSc that I can bind to PrPC to make it be PrPSc.
As my PrPC versions continue to be produced by the cell, my PrPSc versions continue to have proteins to bind to and transform. And the new PrPSc will continue to bind and transform.
Replication without nucleic acids. Adorable, it is not?
And now that I have become this new protein, I am going to break you and kill you.
Let me explain.
PrPSc prions start to increase. You try to degrade them, but you fail. They often aggregate into amyloid-containing plaques and fibrils, which accumulate in your brain.
Your neurons gain cavities (vacuoles) and lose their function. You try to remedy the situation with the proliferation and hypertrophy of neural cells of other types, but you just make a mess.
You say the brain becomes spongiform. Love it.
And it goes on like this for years. Silently. One day, you begin to change.
In the coming months, your senses and sensations will play tricks on you and you will progressively lose control of your body and control of your mind. Bedridden and demented, you will die.
And you do not even bother to fight…No immune response from you is seen.
Perhaps you love me as much as I love your brains. Despite some of them being a bit…disappointing.
PrPSc can exist in a variety of configurations/strains, some of which lead to particular disease presentations.
As PrPSc, I also affect the nervous system of sheep and goats. To the resulting disease you have called Scrapie. You knew that the diseased animals showed spongiform changes in their nervous tissue. When, in the 1950s, you realised the histological similarities between Scrapie and Kuru, a disease (now erradicated) that affected the people of the Fore tribe in Papua New Guinea, you started digging deeper and ended up finding me. So skilled…
But I do not stop here. I also affect cats, mink, kudu, nyala, oryx, moose, deer, reindeer, elk, camels, COWS.
Are you recognising me now?
I will remind you.
Once, you decided to supplement animal feed with sheep-derived components, which included their brains. What some of those sheep were carrying? PrPSc!…
What happens after the ingestion of PrPSc? I reach the lymphoid tissue and peripheral nerves, sites where I replicate and accumulate (but do not harm), while travelling to the central nervous system.
Who ate the feed? The cattle. Guess what happened? The cattle became infected with PrPSc.
An epidemic of prion disease in cattle happened in the 1980s in the United Kingdom. And you have called the cows mad!…Poor things! You also have an exquisite name for this disease: Bovine Spongiform Encephalopathy (BSE).
Who ate the cattle? You. Guess what happened?
Oh, you are so good to me.
About ten years later, as I said would happen, you began to change. More than 200 of you died.
But once again you figured me out, and with a bunch of those sanitary measures of yours, you ruined my game.
So you can tell I have a few ways to bother you. The ones you have found so far:
Within you, I can simply change from PrPC to PrPSc whenever I feel like it.
I can get to you via PrPSc-containing materials:
Using cattle in our beloved food chain
Using other exposures
For example, there was a time when you unknowingly used materials containing PrPSc in your medical procedures and treatments (always amusing me) — transplanted cornea, dura mater and liver; dura mater material in radiographic embolisations; human pituitary hormone; neurosurgical instruments; electroencephalography depth electrodes; blood products.
Meanwhile, you have revised your infection control measures.
And do you remember the PRNP gene that encodes me/the PrP protein? PRNP can suffer mutations.
- The right mutation will cause the encoded protein to be…my PrPSc variant. Surprise!
- Furthermore, there are other PRNP mutations that lead to novel forms of PrP that also cause you a neurodegenerative disorder.
Offspring will inherit a mutated PRNP if it is present in the reproductive cells of a parent. Again, sooo sooorry.
Sometimes I feel you have even bigger plans for me. Once in a while, I sense you talking about me as a possible agent of bioterrorism.
I guess it is up to you, but, who would guess, I am not that interested. At least not for now.
For now, I am happy just for you to be thinking of me when you want to make that brilliant diagnosis for your patient.
And you are becoming aware of prions’ guilt in other neurodegenerative diseases (other proteins that can become self-propagating include, among others, amyloid beta, alpha-synuclein, tau, and huntingtin, each one responsible for different disorders). But you have a long path to walk. And I like to watch you studying about me. I mean, us, prions.
You are also trying to find treatments for prion diseases…You bastards! But you still have not got it right. Let us see what you can come up with. At the moment…you do not stand a chance, my dears.
Well, it is time for me to go.
Thank you very much for your attention.
Enjoy while you still have it.
See you around.
Sincerely yours,
Prioness
(that is a name that I would have liked)
I did not reveal everything that you have already discovered…On the Bibliography page, Infekta lists some references where you can learn more about me. She is also leaving below a feedback form for you to submit if you want to. You can tell me things…