Treatments for Prion Diseases - Help!!

[maybe_zimmel_nadir]

Hi everyone,

I am an (almost) grade 12 student looking for some help with a project of mine regarding prion diseases and treatments involving them. I have been brewing this idea since July 2025, but so far have kept it to myself I am hoping someone is able to perhaps provide their own perspective/expertise on this idea of mine as well any changes/improvements that should be made.


(p.s - There's kind of a lot here...please please PLEASE!! let me know if you have questions )


The birth of the super epic research paper Never Underestimate the Fungi (get it? )
Hsp104 is a chaperone (which is defined as a protein which helps the other proteins) specific to fungi such as yeast. This chaperone is interesting, because rather than preventing the misfolding of proteins like chaperones Hsp40, 70, and 110, by working together, sharing information, etc, it takes the already aggregated proteins and helps it to unfold and keep the fungi safe.

Animals such as humans do not have this certain chaperone, but we do have others such as Hsp 40, 70, and 110 which all help with the disaggregation of prions by stopping them from misfolding in the first place. If Hsp104 is introduced (exogenous Hsp104) from another source, it may be able to team up with these chaperones and promote disaggregation in humans and therefore help with treating diseases associated with amyloids. But, there is still doubt that this would work at all, as scientists worry that Hsp104 alone may not be enough. These limitations may mean that other treatments will have to be used alongside this introduction of a fungal chaperone. However, this does prove that certain chaperones in fungi and humans can work together, and then perhaps lead to certain therapeutic treatments for certain diseases associated with them (amyloid diseases, such as CJD) Leading us to the question...can other parts of yeast (Saccharomyces cerevisiae) be used like this?

What I came up with
Btn2 and Cur1 proteins are able to silence misfolded proteins that can form within Saccharomyces cerevisiae by gathering the prion aggregates in a single location. Btn2 and Cur1 prevent aggregated proteins from dividing into daughter cells, which stops their traits from being passed down, ceasing aggregation within the yeast. This sequestering done by the proteins can help mammalian cells fight off prion diseases as well, however, Btn2 and Cur1 proteins are not present within them. But using the practices of biologics, it is possible to extract Btn2 and Cur1 proteins from saccharomyces cerevisiae, and insert them into mammalian cells within the human brain exogenously. This would sequester those proteins the same way it does in the fungi.

Cell penetrating peptides are one of the simplest ways to introduce exogenous proteins such as Btn2 and Cur1 into mammalian cells. These small peptides attach to the desired protein, assisting in its transportation. The cationic residues on CPP’s (such as arginine and lysine) bind to the phospholipid bilayer of a mammalian cell by engaging with negatively charged glycosaminoglycans (GAGs) such as heparin sulfate and chondroitin sulfate on the surface of cells. Through this bond, the protein which is attached gets engulfed by the cell through endocytosis. From this point, the Btn2 and Cur1 proteins are expected to act as they usually would within yeast cells, and sequester the protein aggregates.

Limitations...
A limitation that exists however, is that these polycationic CPPs like to bind and enter most mammalian cells. This means that the cells we want the protein to bind to, may not get targeted like we want because they are so general. Because of this, the cargo they carry can go to undesirable cells, which could lead to unwanted side effects.

Efforts have been made to make CPPs more specific. An example of this includes cancer-cell activated CPPs. These cells have a few components; Polycationic CPP to penetrate the cell membrane, and polyanionic biopolymer, which binds to the polycationic CPP to stop it from entering healthy cells. The polyanionic biopolymer binds to the cationic CPP and stays linked when no cancer associated proteases are present. This keeps the CPPs from penetrating any cells including healthy ones. But when cancer is detected, it releases a protease, which disconnects the link between the cationic and anionic parts of the CPPs. And they separate, the cationic cells able to penetrate cell membranes. Meaning the cationic cells are able to be targeted specifically by cancer cells and act upon them only.

(Just recently I've been thinking of perhaps resteering this biologics/CPP ideas and looking into aptamers, but I'm not sure yet)

Thank you, thank you, to anybody who read this mammoth of text. Any opinions are welcome!! I'm really looking to expand this project further and locate any gaps in it.