Université Hassan II: Omar Moustafa Hassan El Atal and His Insights #2

Hey there! My name is Omar Moustafa Hassan El Atal, and I'm an undergraduate biology student from Morocco. I'm very passionate about genetics, and I hope to pursue a career in biomedical research. In my free time, I enjoy reading, playing chess, and composing music.

Reviewed Article: Conformationally adaptive therapeutic peptides for diseases caused by intrinsically disordered proteins (IDPs). New paradigm for drug discovery: Target the target, not the arrow by Fantini et al., 2025.

Main Argument & Findings:

Every living thing is built from proteins, which are tiny machines made of long chains of smaller parts called amino acids. The way a protein folds into a three-dimensional shape decides what it can do, just as the shape of a key decides which lock it fits. Some proteins carry oxygen, others digest food, and some send messages between cells.

Usually, a protein folds into a clear, stable shape that lets it do its job perfectly. But here’s something surprising: about half of all human proteins don’t fold into a single shape at all! Some are completely disordered, while others only have flexible sections that stay loose and shift form when needed. These flexible molecules, called intrinsically disordered proteins (IDPs), make up a huge part of our biology. Their ability to shift and move helps cells adapt to stress and changing conditions, but this same flexibility can sometimes cause trouble.

Scientists recently made huge progress in predicting how proteins fold using artificial intelligence. In 2021, this achievement earned the Nobel Prize in Chemistry for the creators of AlphaFold, a groundbreaking AI tool that can predict a protein’s shape from its amino acid sequence.However, even AlphaFold struggles with IDPs, since these proteins don’t settle into one stable form. That makes them especially difficult to study and to target with medicine.

In certain diseases such as Alzheimer’s and Parkinson’s, IDPs can bend the wrong way and form clumps that damage cells. The authors of this article suggest a completely new way to fight these harmful proteins: instead of trying to grab the protein itself, which is constantly changing, why not block the surface it lands on?

With this in mind, they focused on special spots in the cell’s outer covering (the membrane) called lipid rafts. These are small areas made of fatty molecules that help organize communication between cells. Some disease-related proteins stick to these rafts, fold badly, and then create tiny holes that let too much calcium leak into neurons, slowly harming them. Earlier research by the same scientists showed that these harmful proteins carry a short part of their sequence that helps them find and attach to certain molecules on the cell surface. Interestingly, this pattern is slightly different in rodents, which may explain why rats and mice do not naturally develop Alzheimer’s disease: their version of the protein cannot stick to these membrane sites, so the chain of events leading to brain damage never starts.

To prevent this, the team designed a mini-protein called AmyP53, built from small pieces of two harmful proteins, one linked to Alzheimer’s, the other linked to Parkinson’s. AmyP53 rushes to the same rafts first, taking up the landing spot so the dangerous proteins cannot attach or make holes. In laboratory and animal tests, AmyP53 protected brain cells and was even safe when delivered through the nose, which offers a direct route to the brain!

Importance for Youth:

For young readers, this research shows that breakthroughs often start with bold new ideas that are tested with patience and care. It is inspiring to see scientists designing creative ways to stop diseases like Alzheimer’s, but also important to remember that turning a discovery into a safe treatment can take a lot of time. Science needs patience just as much as it needs passion. We may not see this particular treatment in clinics for many years, or even decades, but every careful study brings us closer to understanding diseases like Alzheimer’s and Parkinson’s. By staying curious and informed, we can be part of the generation that supports safe, fair, and responsible science.

What I Learned: 

For me, the highlight of this work was how each discipline filled a gap the others couldn't: modeling, chemistry, and biology all played a part in building AmyP53, and none of them could have done it alone. It brought to mind a letter by Isaac Newton, where he wrote, “If I have seen further, it is by standing on the shoulders of giants.”

It also made me think about what comes next. The authors suggested that their design strategy could extend to other biological structures; might we see the same strategy used for cancers, infections, or metabolic diseases in the future?

Citations: Fantini, J., Azzaz, F., Di Scala, C., Aulas, A., Chahinian, H., & Yahi, N. (2025). Conformationally adaptive therapeutic peptides for diseases caused by intrinsically disordered proteins (IDPs). New paradigm for drug discovery: Target the target, not the arrow. Pharmacology & therapeutics, 267, 108797. https://doi.org/10.1016/j.pharmthera.2025.108797

LinkedIn: https://www.linkedin.com/in/omar-moustafa-hassan-el-atal/

Website: https://omarelatal.github.io/