Protein Folding and Pathology

As a biochemistry major, the nature of protein synthesis has always appealed to me. With regard to medicine, I was quick to attribute common pathologies with abnormalities at the genetic level; however, as a medical student, I’ve become interested in another, equally important factor in creating disease – protein folding.

The essence of biology stems from understanding that DNA is transcribed into mRNA which is subsequently translated into protein(s). If a particular DNA sequence has a mutation, then every protein which is ultimately created from this template will also be messed up. In other words, bad genes make bad proteins (most of the time).

Now let’s consider another scenario. A particular gene is normal; however as the protein is being translated from the mRNA, improper folding causes the protein to assume a shape which isn’t viable. Going one step further, let’s say that this poorly folded protein doesn’t get marked for degradation. It may actually go rogue and cause “normal” proteins to take on an “abnormal” physiology. Prion diseases (like mad cow disease) work in this fashion. Keep in mind, this is all due to a few proteins which simply didn’t fold correctly.

If there was a way to get into the body and help some of these proteins fold up properly, I surmise that the prevalence of certain pathologies would show a marked decrease. No wonder so much research is being poured into mapping out the “rules” for protein folding.

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