Prions-What are they ? Protein Misfolding Mechanism

A prion is an infectious agent composed entirely of protein material, called PrP (short for prion protein), that can fold in multiple, structurally distinct ways, at least one of which is transmissible to other prion proteins, leading to disease that is similar to viral infection. They are suspected to be the cause of transmissible spongiform encephalopathies (TSEs) among other diseases.
In This video the following things have been discussed:
What are Prions ?
How they are made ?
Why normal protein becomes Prion ?

[@nexotim1667]

it is so scary knowing there is such a small yet extremely mortal infectious agent. Not detected by the immune system, no drug or treatment for it, 100% mortality. I find this the scariest infectious agent out there lol.

[@nexotim1667]

@@BeaverdamMan Not everyone realises that there are things far worse than covid. The only difference is that covid is just spreading faster thus atracting more attention. As rare as prion diseases are, imagine an epidemic triggered by these. It would start havoc.

[@nexotim1667]

@@BeaverdamMan if that kind of mass infection was ever intended it would have happend with any other vaccine. Not really a believer of those teories tbh.

[@Tejmurthy445]

@@BeaverdamMan it’s true that the vaccine is an mRNA copy of the viral spike protein and it uses host machinery to make it, but right after your immune system recognizes it as a non-self protein and attacks it, and making sure your body “remembers” it. The ONLY reason why I wouldn’t take the vaccine is if you are 100% you had the infection before and therefore immunity is already established or if you’ve had a history of severe adverse reactions to vaccines in the past-like anaphylaxis. If you’re healthy and have not gotten Covid yet, you should definitely get the vaccine. The mechanism of vaccination is the same as a viral infection-though with less code so the virus cannot reproduce.

[@Minecraftesque]

@@BeaverdamMan CJD is caused by ingestion of meat infected with prions. It is not related to the COVID-19 spike protein. There are different forms of vaccines available to develop an immune response, included weakened virus, dead virus, or mRNA, which creates antigens normally found on the spike proteins in your own body (not infectious or disease-causing). This way if your body does encounter a real spike protein, it can mount a quick immune response and clear it out immediately.

[@Minecraftesque]

@@Tejmurthy445 Even if you have had Covid-19, the vaccine will still help to create a MORE robust immune response. While it is true that people who have had the virus develop an immunity, getting the vaccine is a near-guarantee to prevent the disease in the future.

[@ppartsx]

thank you for explaining the WHY misfolding occurs. I wasnt getting it by just reading wikipedia about it. sounds similar as to why cancer happens sometimes.

[@hussainbiology]

You are welcome.....I am glad that my Lectures are helping.....

[@haniy8817]

@@hussainbiology do you have any reference link to read?

[@thaxolotlfish]

I was having trouble understanding the conversion between its normal form to its scrapie form and this video helped clear that up, thanks. I ended up using this video to help write a section of a paper I'm writing.

[@hussainbiology]

Ah.... Glad to hear that... It really matters a lot when some one is getting a potential help❤️❤️

[@akankshabhatt3357]

Thankyou so much for putting this up and using the colors and diagrams throughout it was so helpful! I had a research paper to read and understand prions from it and it was quite difficult to grasp the major concepts but you did it so well and made it short and simple. Bless your soul!

[@hussainbiology]

thanks Akanksha for appreciation..Glad to know that it helps ✌️

[@bertarissen6568]

Bèta-strands of planar monomers stack on one another with their side chains much more interwoven via hydrogen bonds than in alfa-helices. This fibers aggregate in what is called amyloid. The PrP(Sc) nucleus forms a template and out of the normal PrP pool the misfolding is formed. The answer how this eventually leeds to celldeath is not quite clear, but it is suggested that the large aggregates themselves are not toxic, but smaller aggregates of the same proteins causes the problems. Besides the spongiform encephalopathy we see amyloid plaques also in disorders such as Alzheimer and Parkinson disease.

[@partytilyoupuke321]

By far the best summary I've seen regarding Prions. Well done.

[@hussainbiology]

thanks for appreciation

[@ketansiddhapura4765]

Very well explained. Nonscience student can understand easily in a couple of minutes. Good job.

[@hussainbiology]

Thanks Ketan for appreciation.

[@Luisa-xe1ow]

Thank you!! Our lectures sometimes use such weird wording, that I could not understand what the prion protein actually is. This video makes a lot more sense

[@cybercityoedo808]

Coronavirus: I'm the deadliest being in the universe.
Prion: Hold my Beer

[@JustAnotherAccount8]

I mean, covid was never that lethal, the bad thing about it is that it spreads so quickly to people who have underlying health issues

[@stephenbrand5661]

@@JustAnotherAccount8 Exactly this, nobody’s ever claimed that Covid is very deadly, it’s just insanely contagious and hasn’t been around long enough for us to have significant immunity.

[@missdarkhumour2222]

Nine months later, we see that the spike proteins of the covid2 virus are playing a role in the formation of prions, causing neurological damage. So, it is as bad as they say it is, even if someone “recovers” from infection. Chronic long term side effects from infection are being seen now, and will be even more prevalent two years after the start of this pandemic. I used to be skeptical of the seriousness of this virus-now, not so much. That same spike protein is being used in the vaccines, so don’t think you’re safe there either.

[@yoursnatchedweave641]

@@missdarkhumour2222 do you have sources for what you said? i want to see more

[@missdarkhumour2222]

@@yoursnatchedweave641 There’s plenty of white papers out there. But I’ll give you the link for the RUclipsr that opened all the sources online for all of his viewers to see. Hold on...I’ll send the link in another comment reply.

[@prism2451]

Im not a biology student but i find it interesting

[@hussainbiology]

thanks for appreciation.

[@peachbeach9471]

Same

[@vacilated]

But I am😶

[@ankitayadav1123]

Aap dhanya Hain Prabhu 🙏. Thank you so much for this awesome video ♥️
And it is really "Alll about Prions." You don't need to search it anymore 😁
Thank you so much

[@hussainbiology]

Thanks Anamika for appreciation, Glad to know that it helps.........And may be it might not be all about Prions but certainly it is sufficient. Thanks

[@Medicolifeshorts]

You have done justice to it's explaination.... Salute sir

[@hussainbiology]

thanks Dr Asma... Glad u like it...

[@ween8457]

saved me for my exams u legend

[@hussainbiology]

thanks Buddy for appreciation... Really Glad to know that it helps.....

[@Dang3rMouSe]

Excellent explanation. The prion infection spread here in the US among our massive deer population (Chronic Wasting Disease) is a serious issue imo. Though rare at this time there's already evidence of deer>human transfer from eating infected deer meat which originally was thought not possible unless brain or spinal tissue was consumed.
Our rural human population has a long tradition of supplementing their diet through hunting wild game, mainly deer. The US fish & game agency is trying to find ways to stop the spread but they don't have enough resources, can't get ahead of it & it's spreading like a wildfire. A quick test for hunters to test their harvested deer is needed to prevent humans from developing what often appears as CJD. Hopefully this will get the attention needed before it's too late.

[@FranciscoTC]

The information on this video is correct however much simplified.
While PrPSc is sometimes resistant to protease degradation, this is not true in many cases and has been shown NOT to be related to presence of disease.
The mechanism of transformation is actually thought to be multifaceted, one way it occurs is through templated transformation where PrPSc aggregates and leads already formed PrPc to become misfolded, this is present in both genetic and infectious forms of the disease, and accounts for its rapid progression.
Another way is the spontaneous misfolding of PrPc into PrPSc which is more thermodinamicaly stable, meaning, if PrPc is not stabilised by its usual GPI-link to a cellular membrane, it will tend to misfold into PrPSc to achieve a lower state of energy.
Regarding the mechanism of toxicity and cell death, it is thought it occurs in at least two different ways: One is that the bonding of PrPSc to membrane PrPc leads to NMDA overproduction with consequent synaptic disfunction and cell death. Another way is the accumulation of PrPSc in the ER and Golgi which lead to activation of pathways that inhibit translation in the cell, leading to its eventual death.
There as been much progress in recent years regarding prion diseases since this video came out and i encourage the viewers to read on it, as it is a very interesting topic.

[@kingseiryu929]

Thanks for sharing. I read that long term covid 19 symptoms correlate with the neurodegenerative effects of prion diseases. Is there a link?

[@synthwavespartan2808]

Damn.... now if only we knew of a way to cure or fix it...

[@arturzaduryan6108]

Hello! I'm desperately trying to find clues to the molecular mechanism of prion replication: how do misfolded (scrapie form) PrPs actually catalyze misfolding of the normal cellular PrPs on molecular/biochemical level? I understand that it is not completely cleared out, but I couldn't find any molecular/biochemical hypotheses. Also, what is the biochemical reasons for which such saturation with beta-sheets renders PrPsc protease-resistant? Isn't there really any proteases specific enough to degrade high beta-sheet-content proteins? Or does it have to do with relatively rapid formation of amyloid fibers? Or does it have to do with chaperon malfunction (thus potentially mutation in chaperon genes as well)?
Thanks!

[@hussainbiology]

Well in my understanding , i can say if a single function goes missing in the body it leads to some pathological states.........
First point is the Chaperone are not able to make it correct back,,, and why it is so is still unknown.
Second point is that Why Beta Sheets render it protein resistant ,,,,,,,,it is still unknown but i think this might work here
The side chains from the amino acid residues found in a β-sheet structure may also be arranged such that many of the adjacent sidechains on one side of the sheet are hydrophobic, while many of those adjacent to each other on the alternate side of the sheet are polar or charged (hydrophilic), which can be useful if the sheet is to form a boundary between polar/watery and nonpolar/greasy environments.

[@SebastienWolfe]

Thanks Hussain. Great video.

[@hussainbiology]

Always at ur service..........It makes me happy that i am doing something good for others,,,,

[@smiggyballs4100]

as soon as i heard the indian accent i knew this would be an informative video

[@Cherryhaeeee]

Thank you for saving me

[@aanaelsa5703]

Literally enjoyable= you made it so simple and a very basic concept interesting. Watched your videos for the first time. Keep it 👍 goood luck for a great future ahead

[@hussainbiology]

thanks Aana for appreciation..Glad to know that it helps ✌️

[@aanaelsa5703]

@@hussainbiology can you plz upload some videos on basics of genetics?

[@hussainbiology]

@@aanaelsa5703 Hi Aana , i have already put out some videos regarding What allele is ?
✓ Gene flow
✓ Gene interaction
✓ Basic of Central dogam
✓ Overview of Replication , Transcription , Translation and many more.
I suggest you to see my playlists where u will find sorted videos into categories.

[@aanaelsa5703]

@@hussainbiology okay.sure thankx😊💐

[@hussainbiology]

@@aanaelsa5703 You are welcome ✌️

[@kb8330]

Thank you for helping with your video to understand what prions are. This was a good video for students learning from visuals

[@hussainbiology]

thanks for appreciation...Glad to know that it helps

[@saipawans2574]

My teacher is using your videos to teach basics appreciate your effort damn good videos ...I am a huge fan of notes and pictorial representation ...

[@hussainbiology]

thanks for appreciation

[@dannydaily20]

Great knowledge In little time.. thanks bro.

[@hussainbiology]

So nice of you

[@baroganti]

THANK YOU! Very well presented and explained, life saver!

[@hussainbiology]

thanks for appreciation..Glad it helps ✌️

[@maxziegler6650]

thank you brother youre the best at this

[@brpawankumariyengar4227]

Great video ....thank you very much

[@hussainbiology]

thanks for appreciation

[@captainniraj3458]

thankxs buddy .explained very well .expecting more such amazing and detailed videos from u !!!!!!!!!!!

[@hussainbiology]

Most welcome! keep sharing and supporting

[@leerunion519]

I am both educated and scared. Thank you..

[@hussainbiology]

😁

[@dmbms]

Thanks

[@descipher]

Thank you sir it was so easy to understand.

[@alvarogarcia9410]

Terrific! I got it so clear, thx!

[@mr_dharsan361]

நன்றி

[@priyakamboj5850]

Thanku so much for sharing such a precious knowledge.

[@hussainbiology]

Most welcome.. Keep sharing and supporting

[@priyakamboj5850]

@@hussainbiology yes sure

[@J.Green-Rx]

There are 7 prion-like domains in the S1 part of the spike protein in the vaccines.
The abstract from the paper "A Potential Role of the Spike Protein in Neurodegenerative Diseases: A Narrative Review" goes into detail.

[@ahmedislam_z2871]

Thank you 🙏🏻❤️❤️

[@hussainbiology]

my pleasure

[@thenightking7167]

Excellent video. Thank you very much.

[@yuvarudra6602]

Hussain Bhai Thx V Much
😁

[@hussainbiology]

thanks for appreciation..Glad it helps....✌️

[@CountGrishnakh]

I have a question. How exactly does a prion 'infect' other proteins to make them misfold? Aren't prions non living things? I read somewhere that they have no organelles or nucleus. If it isnt alive, how does it infect other healthy prions?

[@hussainbiology]

First of all , before you counter me with another question let me tel you that the pathophysiology of Prions is still not clearly understood and is still ambiguous.
Now your questions.
Prions are simply proteins with basic amino acid core structure like other proteins but when these Normal Prions turn into abnormal Prion protein at that time they are termed as infections since these Prions are present mostly on the surface of Neurons.
So we can say it is the Transformation of Prp c to Prp Sc that makes them leethal.
So when and how Normal prion protein becomes abnormal , it is when protein aggregates more Beta sheets than alpha helices then we say it has become abnormal Prion since it is now resistant to degradation and also gets misfolded.

[@CountGrishnakh]

Thanks for replying and answering my questions,
I have two more:
1) In your video, you mention that some Prion Proteins are resistant to proteases. what causes this resistance?
2) How do the Prp Sc infect other Prions as well (what's the science behind that process?) ?
Thanks

[@hussainbiology]

The presence of 43% beta sheets aids to the resistant properties of Prions.
Secondly the Abnormal Prions hampers the process of folding of other proteins , that renders them non functional.

[@M4MBBS197]

as any amount of misfolded protein stuck in ER it eventually developes ER stess that is the main pathway of cell death

[@jformaldehydem]

So this means that a misfolded protein can't encounter an already fully formed protein and cause it to denature? Because that is what I always thought happened, but if I understand you correctly, that makes much more sense.,

[@CompilingInput]

Nice video, i am just here out of curosity... gr8 vid, wish the concept had actulal animation 👍😉

[@hussainbiology]

thanks for appreciation..Glad to know that it helps

[@uchiha_itachi7644]

It was a great help I wasn't able to understand this part only , Thanks a lot! ❤️

[@hussainbiology]

thanks for appreciation..Glad it helps ✌️

[@patelshalini8549]

Yur teaching style is interesting sir

[@hussainbiology]

thanks for appreciation

[@choykage26]

Subscribed. Thanks for the video!

[@georgeswan580]

Very good summary

[@hussainbiology]

Glad to know , that my videos are good........Thanks

[@Jindy2]

This is excellent. Thanks so much for your clear, easy to follow explanation.

[@hussainbiology]

thanks for appreciation..Glad to know that it helps...

[@massimoazzano]

Please could you have a look how heparin combine with spike proteins to generate prions?

[@setme4ree]

Is prions in the vaccine

[@user-qx6nh6sj2s]

Thank you so much this is very helpful💚💚

[@hussainbiology]

Thanks for appreciation...Glad to know that it helps.

[@mystarfield]

Really nice presentation :)

[@maka4164]

Thank you so much for this, I had to cram this topic for my reporting tomorrow and I had a hard time understanding the book, thank goodness I found this 🥹

[@hussainbiology]

thanks for appreciation..Glad it helps..

[@MariVierr]

Thank you, very helpful construction of informations 🌹

[@ishansharma6890]

excellent explanation

[@hussainbiology]

Thanks Ishan for appreciation..

[@vtron9832]

I understand that these Prions are too simple and basic (to the point of not even containing genes) to be considered alive. But I think, that anything that is capable of replication is alive. From how I see it, the definition of life is molecules that are able to turn inanimate matter into exact or similar forms of themselves. Cells, viruses and viroids do this with genes, but if prions can do it as proteins, then I consider them somewhat alive too. What do you think?

[@hussainbiology]

Hi sir
When we see Molecules...we state these are non living things but when Molecules function together in a coordinated manner they become a cell.
So in order to call Prions alive they should have other molecules to work with .
And Prions don't replicate , Prions (Prion proteins only poke other proteins and make them prions also , like Prions disrupt thr folding pattern of other proteins)

[@hussainbiology]

Life is mystery , and may be someday ur statement will become true regarding the aliveness of Prions

[@Hugo-qp8yu]

good vid

[@tehShikari]

Love it! A great and simple explanation, with great visuals! Thank you sir!

[@hussainbiology]

thanks for appreciation..Glad it helps ✌️

[@franklinclinton7561]

Awesome video!

[@hussainbiology]

Thanks for appreciation....Glad to know that it helps

[@irfanhandono]

I get a feeling some people in the future might develop prions which can spread very fast and deadly.

[@williamhornabrook8081]

My grandfather wrote the definition of the prion Kuru.
I kind of want to see if it's possible to synthesize such a protein.

[@chandnikhan2549]

Really nice video

[@hussainbiology]

thanks for appreciation.....

[@Atifaziz518]

In prions Abundance in beta sheets cause resistance against proteases. What's the reason behind it??which thing make it resistant in beta sheets towards proteases??

[@hussainbiology]

Why Beta Sheets render it protein resistant ,,,,,,,,it is still unknown but i think this might work here
The side chains from the amino acid residues found in a β-sheet structure may also be arranged such that many of the adjacent sidechains on one side of the sheet are hydrophobic, while many of those adjacent to each other on the alternate side of the sheet are polar or charged (hydrophilic), which can be useful if the sheet is to form a boundary between polar/watery and nonpolar/greasy environments.

[@miguelrodriguezvassallo993]

Excellent! It helped me a lot! thanks!!

[@hussainbiology]

thanks for appreciation

[@iftikharhussain3168]

great job done carry on plz

[@hussainbiology]

thanks Iftikhar for appreciation....Glad to know that it helps

[@rohanmarde9303]

Where can I learn more about current research being done about prions?

[@hussainbiology]

NCBI

[@WetaMantis]

For once a video from India that has both an English title and the whole video talking in English 👍

[@WetaMantis]

Great vid!

[@Micro-life]

✌✌✌nice package in few minutes😊😊😊...thnku sir

[@hussainbiology]

thanks for appreciation......😊😊😊

[@chetankumar-ch2su]

Good job bro...

[@hussainbiology]

Thanks Chetan for appreciation...

[@ezpzwins7613]

How do they replicate ?

[@massimoazzano]

Is the spike a prion?

[@sabasadiq5735]

Thanks.. 😍

[@hussainbiology]

most welcome

[@webecamefire666]

I read that the person that discovered prions said specifically that it is pronounced "pree-on". I personally think "preye-on" is better but I just found this out yesterday so I am surprised Im not the only one saying it like that.
Its just like Gif and Jif I guess 😂

[@johnqpublic2718]

I’m here trying to learn more about Chronic Wasting Disease and its destruction of North and South American Cervidae populations.

[@usmanbhatti2001]

also tell us about amyloid disease

[@hussainbiology]

Surely U will find the video of same disease soon...

[@analystalagurin304]

can i ask if what book u read? thank you!

[@hussainbiology]

I read Alberts Cell Biology and Lodish Cell Biology mostly.

[@alvarogarcia9410]

do you have any bibliography??

[@hussainbiology]

Lodish Cell Biology

[@tijomathew3119]

Great job keep it up. Ur lit asf

[@hussainbiology]

thanks for appreciation...Glad to know that it helps

[@ehSamurai3483]

So can a human make his/her protease stronger so that PRPsc can't resist it?

[@youmustknow8.5M]

Sir please told in Hindi it more understanding

[@robertpaulson4151]

Why is there no public outcry or war on prions?

[@TheGiu77]

Could the Spike protein become a prion in the unvaccinated body? Like, the vaccinated in the acute phase, transmit to their children and lactating women? And that protein becomes infectious and liver-preferred?

[@SalmanAli-ml6gy]

perfect

[@morphlingpar2549]

INDIANS ARE SMART ♥️ LOVE FROM CHINA 🇨🇳

[@AliceNLi]

Amazing!

[@dinnernoc6289]

I heard it also turns people into zombies?

[@syedamubeen2008]

please upload
reversible binding protein
lipid chemistry, classification, nomenclature of fatty acids
nucleotides and nuclein acids
enzymes
mechanism of enzym action
buffer solution

[@hussainbiology]

Nice to hear the bunch of questions....
Syeeda the above topics are pretty good to put on video but it will take time.
InshaAllah I will make sure to make videos on the above topics.

[@syedamubeen2008]

thank you so much :-)

[@hussainbiology]

I am having tight schedule these days ..😊
Always here to help

[@vuan8393]

jazakallah

[@hussainbiology]

May Allah reward u too..✌️✌️

[@protaties]

Imagine incorrectly constructing a computer and accidentally making it a killing robot.

[@saagha9623]

Is it eukaryotic or prokaryotic?

[@neetaspirants4891]

Sir please aap Hindi mein lecture banaya kare

[@tonyh1345]

The perfect bioweapon would be a prion
Think about that

[@hussainbiology]

yeah

[@ig_baaz_2799]

It is very interesting but if sr represent prions by pictures

[@hussainbiology]

thanks for appreciation

[@myraalina4934]

Thankkkkkkkkkkkkkkkkkkks so much 😍😍😍

[@hussainbiology]

You are welcome Maryam...Keep sharing and supporting,

[@nhule2663]

Thank you 😭 ❤️!

[@hussainbiology]

You are welcome.... Keep sharing and supporting ✌️

[@thefenerbahcesk4156]

Anyone else using yeast to study prions?

[@drspastic]

i wish this were dubbed in English

[@diegorubim8095]

CANABIDIOL FOR PRÍONS

[@user-jd1cg9tv5c]

И болезнь, очень страшная сравнимая с вирусом бешенства.

[@sd91499]

Mad cow disease in cows, CWD in deer, Scrapie in sheep, Kuru in humans

[@JH-no8sy]

CJD and FFI as well

[@zaffariqbal5933]

Are u kashmiri brother

[@hussainbiology]

Yes brother..✌️✌️

[@ERGO288]

Who's here from plague inc.?

[@haivannguyen6812]

I do not understand a thing you said, sorry

[@hussainbiology]

Apologies......May be turning on automatic subtitles will work....

[@StefanOsfit]

Oh no these prions are not good they can have a negative effect on us!!

[@user-jd1cg9tv5c]

Они самые быстрые убийцы, убивают человека за месяц