An organism's protein
s are the machines that make it work, that make it alive
. Generally speaking, when there's any problem with those protein
s, there'll be a problem with the whole organism
. All genetically transmitted disease
s are caused by some certain protein that is exhibited too much, too little, or is badly formed. Even in absence of a genetic disease
, to work properly proteins must fold
into the certain shape that nature has determined, their native conformation
. Most of the time this isn't a problem -- proteins naturally seek out their native conformation due to Anfinsen's Dogma
. However, certain circumstances can cause proteins to unfold and refold tangled in an aggregate
lump with each other, or cause them to fold the wrong way when folding.
When a protein is completely folded or unfolded, it acts chemically neutral. It mostly doesn't bond with other molecules, and it's generally not attracted or repelled by other folded or unfolded proteins. However, when it's in-between, in the actual process of folding or unfolding, it becomes "sticky" -- it tends to attract other partially folded proteins, and become entangled with them. For instance, the white of an egg is a liquid made up of various proteins, and when cooked the proteins all unfold and mix together. When allowed to cool, the proteins refold tangled up, forming the hard, edible fried egg texture that we are used to. While this may be delicious on the blue plate special, in the laboratory the result of this process is called an aggregate, and is often found with sad scientists' failed experiments.
We've known for quite a long time that Alzheimer's Disease was associated with buildups of neuritic plaque -- globs and fibers of hard, insoluble material in the brain's neurons. For most of that time, it wasn't known if these plaques were the cause of Alzheimer's, or a secondary effect of whatever was causing the primary damage. It turns out that amyloid precursor protein is broken down by the body into a very small (40 amino acids long, actually) protein called Ab. This protein is usually soluble, but with Alzheimer's the Ab proteins begin to accumulate together in insoluble amounts. The harmless Ab becomes the disease-causing plaque.
Interestingly, it appears that the crucial step -- the reason Alzheimer's often takes 70 or 80 years to come on -- is the establishment of the plaque. That is, Ab doesn't tend to accumulate at all by itself, it needs other Ab plaque to become entangled in. Much like ice, where crystallization will occur much more rapidly if subzero degree water is seeded with ice crystals, amyloid plaques grow more rapidly when there's something to attach to. It remains to be seen where and why Ab proteins start accumulating in the first place, but once we find the cause we should be able to stop Alzheimer's Disease for good by blocking it.
Diseases caused by prions, like Mad Cow / Creutzfeldt-Jacob are also, in essence, protein folding disorders. These are caused by a certain protein, named PrP, that will stay in a mis-folded conformation (PrPsc) if encouraged to go into it in the first place. In most people, the PrP protein folds normally, leaving the person healthy. Rarely, a mutation in the PrP gene will allow the protein to be made incorrectly, and it will fold incorrectly, making a PrPsc prion. These prions, when exposed to PrP which is in the process of folding, will encourage that PrP to fold badly too, thus creating another PrPsc. While PrP can be processed and cleaned out of a cell once it has been used, PrPsc is shaped differently enough that it can't be, so it never goes away. PrPsc, much more quickly than with Ab in Alzheimer's, builds up into plaques, handily destroying whatever nervous tissue it's building up in. See the writeups under prion for more on this.
Besides building up un-processable plaques, protein folding errors can leave behind too little of the effective conformation for it to do its job. This is the case with diseases like Cystic Fibrosis, and many other hereditary diseases. Cystic Fibrosis results from lack of a protein that regulates chloride ion transport through a cell membrane. Findings show that while this protein seems to be forming correctly, there is a problem with one of its associated chaperone proteins. Chaperone proteins help encourage unfolded proteins to fold in the right way by surrounding them and protecting their movement. In Cystic Fibrosis, the chaperone doesn't pull away from the transport protein smoothly, leaving it partially mis-folded and useless. The broken chaperone protein then moves on to do the same thing to another transport protein, and so forth.