Hello everyone and welcome to this week's blog post where we will be discussing prions. In this article, I will explore what prions are, before examining how they cause disease. I will then explain what Creutzfeldt-Jacob disease is, before finally discussing the problems with creating treatments for prion diseases.
Proteins are a type of polymer, consisting of a chain of amino acids bonded together with peptide bonds. The chains of amino acids can then fold themselves and form bonds between non-adjacent amino acids (e.g. hydrogen bonds, ionic bonds, hydrophobic interactions and disulfide bonds), forming a specific 3D shape. This specific shape allows the protein to perform useful functions in the organism, such as acting as enzymes or receptors.
One of these types of protein is called prion proteins. While the exact function of these proteins is unknown, we do know that they are found in the cell membranes of most cells and may play a role in the transmission of messages from the body to the brain.
Sometimes, however, the production of these prion proteins has errors, causing the protein to become misfolded and thus changing the protein's function in the organism. While these proteins usually get detected and broken down by the body, sometimes they escape detection and build up in the brain.
There are numerous diseases which these misfolded proteins (prions) cause. This family of rare diseases is called 'transmissible spongiform encephalopathies'. As prions accumulate in the brain, these diseases are all neurodegenerative disorders, and thus have some similar symptoms, including dementia and loss of brain function.
When prions build up in the brain, they cause other proteins in the brain to misfold and become prions as well, causing the exponential growth of the number of prions in the brain. This cascading effect helps explain why prion diseases have a long incubation period but are very quick to kill the organism they infect after the onset of symptoms occurs.
Creutzfeldt-Jacob disease is a type of prion disease, which affects approximately 7000-8000 people each year worldwide. Unfortunately, Creutzfeldt-Jacob disease is always fatal, as there are currently no treatments to cure or control the disease.
Creutzfeldt-Jacob disease is caused by prions accumulating in the brain. As described above, this leads to brain cell death, resulting in small holes developing in the brain. This damage then results in the symptoms of Creutzfelt-Jacob disease, such as dementia, loss of balance and coordination, changes in personality and loss of motor function. Eventually, the disease leads to death, usually within a year of the symptoms starting.
While we don't know exactly what causes prions to form, there are 4 types of Creutzfeldt-Jacob disease (CJD), which are each caused in a different way. The first is sporadic CJD, which is caused when a prion in the brain folds incorrectly.
Meanwhile, variant CJD is usually caused by the consumption of beef from a cow which was infected by 'mad cow disease' (another type of prion disease which affects cattle). It is thought that these two diseases are linked, as prions from the infected cow can be transmitted through infected meat and cause disease in humans.
The third type of CJD is called familial CJD. As we explored earlier in this article, each protein has a unique sequence of amino acids, which is defined by the order of bases in DNA. As such, prions can be caused by mutations in DNA which cause the protein to be formed incorrectly. Furthermore, the mutated gene is dominant, meaning that if one of your parents has the gene, you have a 50% chance of inheriting it.
Iatrogenic CJD can also occur, which is where prions are spread between people during medical or surgical treatment. It is important to note that prions can not normally spread between people, as they are found in the spinal fluid and brain tissue. Nonetheless, transmission between people can still occur in rare cases. This is usually due to the transplantation of corneas and grafts of dura mater. To combat this, organ donation is now banned for anyone who is infected or suspected to be infected with CJD.
In addition, some cases of iatrogenic CJD have also be traced to the injection of contaminated pituitary growth hormone. In response, once this link was discovered in 1985, all human growth hormone is now synthesised artificially, thus eliminating CJD transmission by this route.
The term 'prions' has been around since 1982 when Stanley Prusiner of the University of California correctly hypothesised that some diseases, such as mad cow disease and Creutzfeld-Jacob disease, were not caused by traditional infective agents, but by misfolded proteins. Nonetheless, despite lots of research being conducted since 1982, we still do not have a cure for any type of prion disease. Instead, treatment for the disease focuses on easing symptoms and providing support.
One of the reasons for this is that prions are not caused by typical infectious agents, like bacteria and viruses, so antibiotics and antiviral drugs are ineffective against them. Furthermore, the development of treatment against prion diseases is made even harder due to the rarity of the disease. This is because funds for research are limited and there are only a small number of patients who can be part of clinical trials to test new therapeutic treatments.
At the moment, research is focusing on gaining a better understanding of the cellular mechanisms involved in the formation of prions. If we know more about the formation of prions, then it is possible that we can find a treatment which disrupts this process and prevents prion diseases. Additionally, other research projects are focusing on how prions cross the blood-brain barrier, in an attempt to find new ways therapy can be performed.
Moreover, some vaccines for prion diseases are also being studied. While these vaccines have shown some success in trials with mice and with deer, it is unlikely that these vaccines will see widespread use, even if they successfully pass clinical trials in humans. This is because prion diseases are incredibly rare. As such, vaccination against prion diseases is likely to cause more harm than good, as the vaccines may have significant side effects and would only be preventing a very rare disease.
In conclusion, the chance for a cure for prion diseases is slim. Since prion diseases are caused by faulty proteins, they are much harder to treat than viral and bacterial infections. Additionally, since prion diseases are rare, funding for research into the prevention of the diseases is limited. Further, as the incidence of prion disease is low, governments should focus on preventing transmission of the disease, such as by banning organ donations from people with the disease or ensuring that abattoirs test cattle for 'mad cow' disease before the meat can be sold.
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