Effect of Altered Prion Protein on Brain Cells:

Prion protein diseases as neurodegenerative diseases along with the video on the impact of prion proteins on brain cells, got me thinking about how these mutated protein structures have the ability to affect certain functions controlled by our brain and how this process occurs.
Prion proteins so potently affect our brain function because the normally occurring prion protein is found in our brain cell membrane. However, the deformed structure of this protein is poisonous for brain cells. I read an interesting article on research conducted by Adriano Aguzzi, that describes the entire process as being controlled by a ‘switch’ that the prion protein has, which controls its toxicity. This switch covers a small area on the protein’s surface and if another molecules comes into contact with this switch, it immediately triggers cell death.
Prion protein molecules consist of two functionally distinct parts: a globular domain, which is tethered to the cell membrane, and a long, unstructured tail. This tail is vital to the prion protein because it dictates the functioning of our nerve cells. However, in an infected prion protein, this tail serves the opposite purpose as it comes into interaction with the globular part, triggering the ‘switch’ and leading to cell death.
Therefore, this has led to a groundbreaking conclusion for prion disease cures. It stresses the importance of the prion tail in these diseases as it causes cell death. It also suggests that prion proteins with a trimmed version of the flexible tail cannot damage brain cells, even if their switch has been recognized by antibodies. If the tail is bound and inaccessible using a further antibody, activation of the switch can no longer trigger cell death. These findings reveal that only antibodies that target the prion protein tail are suitable for use as potential drugs. By contrast, antibodies that trip the switch of the prion are very harmful and dangerous.