Proteins With Altered Conformations As Agents Of Disease

Prions have been described for some time in the literature, and certainly are known to the public as Mad Cow Disease. You can read more about prions here.

PDB generated prion image

One of the vexing questions about prions is dose, or more simply is there any threshold amount of material contaminated with prion proteins that might be safe? Prions themselves are very tough and stable proteins. Unlike more other infective material that the public is familiar with, there is no safe way to “cook” meat contaminated with prions that will make it safe for consumption.

With this in mind a research group is looking to see if there is such a threshold dose. Using concepts cribbed from toxicology a lab has looked to see if there is a dose low enough at which prion exposure would not lead to disease. You can read the original paper here, but the take home is that there is no safe dose.

When we were looking through the literature on protein folding diseases, a second paper lept into the light, a recent Tau paper, describing the spread of a misfolded tau protein along the intertwined pathways of neuronal cells. This phenomenon is called “tauopathy”; the progressive spread of misfolded tau protein along specific routes through the brain. This pathology is associated with the development of Alzheimer’s disease. One of the unique findings to this work is the decoding of the spread from one spot to another, involving the jumping of the misfolded protein from neuron to neuron.

Though not yet reproduced this finding holds much promise for future Alzheimer’s disease therapeutics as the protein’s march from cell to cell may provide a weak spot in transmission, allowing us to halt the spread of the misfolded protein, and the progression of the disease.

I am asking the Molecular Toxicogenomics students to  write up a post describing how misfolded proteins can be the agents of disease, so if you are interested in the topic, click on through to the comments to get involved in the discussion.