3.9:
Fibrille amiloidi
3.9:
Fibrille amiloidi
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to identify cellulose, and concluded the deposit was some type of carbohydrate. He named the deposits amyloid from the Greek word amylon and the Latin amylum for starch. Even though Friedrich and Kekule discovered the aggregates were mostly protein, only a few years later, in 1859, the misnomer continues to be used. Originally, fibrils were thought to form only outside the cells, but more recently, amyloid has been shown to disrupt intracellular functions.
Amyloid disorders are associated with different protein aggregates. Despite the differences in the amino acid sequences and structures of the disease-causing proteins, a characteristic feature of amyloid fibers is stacked β-sheets. The formation of these insoluble fibrils from soluble proteins occurs through the production of a partially unfolded intermediate. This intermediate is thermodynamically unfavorable and rapidly progresses to a stable polymer.
Fibrils and other aggregates, like plaques, are characteristic features of diseases such as Alzheimer’s and Parkinson’s. However, the exact mechanism of neurodegeneration and whether the fibrils are the cause or a symptom is still being debated. Other diseases associated with amyloid fibrils are prion diseases, a group of fatal neurodegenerative disorders known to affect animals and humans. They are also known as transmissible spongiform encephalopathies (TSEs). These disorders can arise spontaneously via an inherited mutation and can be transmitted to others by way of infection. A typical example of prion disease is Bovine spongiform encephalopathy, also known as mad cow disease, a neurodegenerative disease in cattle. This disease can be transmitted to humans that consume the infected meat, where it is called Creutzfeldt-Jakob disease.
Suggested Reading
- Reynaud, E. Protein Misfolding and Degenerative Diseases. Nature Education (2010), 3(9):28
- Chiti F, Dobson CM. Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade. Annu Rev Biochem. (2017);86 27-68.
- Cobb, N. J., & Surewicz, W. K. (2009). Prion diseases and their biochemical mechanisms. Biochemistry, 48(12), 2574–2585. https://doi.org/10.1021/bi900108v
- Rambaran, R. N., & Serpell, L. C. (2008). Amyloid fibrils: abnormal protein assembly. Prion, 2(3), 112–117. https://doi.org/10.4161/pri.2.3.7488