Amyloidosis is a rare disease that results from the buildup of displaced proteins known as amyloids. When proteins dissolve in water to become amyloids, they become insoluble and deposit in organs or tissues, disrupting normal function.
Three Types of Amyloidosis
There are four main types of amyloidosis, each due to the deposition of a specific protein.
1. The most common type is AL amyloidosis, caused by the deposition of light chain proteins produced by plasma cells in different disease states.
2. The second most common is AA amyloidosis due to the accumulation of S amyloid A protein or SAA, which occurs in association with chronic infections - e.g. tuberculosis - or inflammatory illnesses such as rheumatoid arthritis.
3. The third type is due to the deposition of a genetically defective or normal form of a protein called transthyretin.
The cells in the body have two different ways of making proteins. Some proteins are made of one single piece or sequence of amino acids; in other cases, protein fragments are produced and these fragments come and join together to form the whole protein. Such a protein can sometimes fall apart into the original protein fragments. This process of "flip flopping" happens frequently for certain protein types, especially the ones that cause amyloidosis.
The fragments or actual proteins are at risk of getting displaced as they are synthesized, to make a poorly functioning protein. This causes proteolysis, which is the directed breakdown of proteins by cellular enzymes called proteases or by intra-molecular digestion; proteases come and digest the displaced fragments and proteins. The problem occurs when the proteins do not dissolve in proteolysis. This happens because the displaced proteins sometimes become robust enough that they are not dissolved by normal proteolysis. When the fragments do not dissolve, they get spit out of proteolysis and they aggregate to form oligomers. The reason they aggregate is that the parts of the protein that do not dissolve in proteolysis are the β-pleated sheets, which are extremely hydrophobic. When they are exposed to water, these hydrophobic pieces tend to aggregate with other hydrophobic pieces. This ball of fragments gets stabilized by GAGs (glycosaminoglycans) and SAP (serum amyloid P), a component found in amyloid aggregations that is thought to stabilize them and prevent proteolytic cleavage. The stabilized balls of protein fragments are called oligomers. The oligomers can aggregate together and further stabilize to make amyloid fibrils. Both the oligomers and amyloid fibrils are toxic to cells and can interfere with proper organ functioning.