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Prions: Brain Wasting Killer Proteins

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Prions: Brain Wasting Killer Proteins Untreatable non-viral diseases: Scrapie, Kuru, Mad Cow, Creutzfeldt-Jacob Prions: brain wasting killer proteins rion research in the last P century has been a puzzling challenge for infectious disease researchers. It has complicated how we define an agent of disease. By Christopher Massey The recent endemics of prion- based diseases such as Bovine The primary mode of Spongiform Encephalopathy infection is through ingestion (BSE) and Transmissible of prion-contaminated matter. Christopher Massey is the Spongiform Encephalopathy Some are infected through a Research and Development (TSE) have caused much genetic mutation of the prion Manager at Hardy anxiety for regulatory protein (PrPc normal, and Diagnostics. agencies that govern PrPsc mis-folded). Normally agriculture and food services. PrPc is water soluble and He earned his Bachelor’s degree in microbiology at The idea of a prion, an harmless. When mis-folded, Cal Poly in San Luis amalgam of PrPsc is water-insoluble and Obispo, California. “Proteinaceous Infectious can aggregate. Prions tend to Particle,” is a frightening build up as amyloid plaques in At Hardy Diagnostics, concept. brain tissue as more and more Massey is responsible for the development of new protein is mis-folded, causing products, as well as the Prions are mis-folded proteins damage and the characteristic refinement of existing ones. found in biological systems. sponge-like texture of infected Every day, numerous pilot These mis-folded proteins tissue. studies to test new formulas then induce the mis-folding of are being tested at the R&D laboratory. other prion proteins. This causes the infected Infectious prions are highly individual to lose motor stable in their mis-folded form function and experience and are thusly resistant to convulsions and dementia. many denaturing agents and heat treatments. The incubation period for a Hardy Diagnostics prion disease can be as long as 5 to 50 years, and there are In the 1920s, scientists by the that when a tribe member no known treatments. name of Hans Creutzfeldt and dies, the Fore men were Alfons Jakob independently allowed the choice parts of the The first records of prion first described a prion disease body (meat) while the woman, infection go back to the 1700s in humans (Creutzfeldt - children and elderly were left in Great Britain. This Jakob disease, CJD). CJD was the scraps, including the “Scrapie” disease caused characterized as a brain, which contained the sheep to experience great neurodegenerative disease in infectious prions. itchiness. The sheep would which the patient has brain then “scrape” against trees tissue which develops telltale However, there is doubt and fences to try to relieve the “holes” and a “sponge-like amongst some anthropologists itching, thus giving the texture.” Of course, they had and biologists that disease its name. Eventually, no idea what the causative cannibalism was ever the sheep would lose the agent was, but this was the practiced by the Fore people. ability to walk and would first recorded description of experience seizures before prion infection in humans. dying. Perhaps the most classic Little was learned about the epidemiological studies of disease until 1936 when J. prion-based disease in humans Cullie and P. Chelle were done investigating the discovered that Scrapie is Kuru disease of a native transmissible through intra- Papua, New Guinea tribe ocular injection of cerebral called the Fore during the spinal fluid from infected 1950s. “Kuru” roughly animals. Further studies translates to “shivering from Figure 2: It is estimated that 2,500 members of showed that whatever the fear or cold” (in the native the cannibalistic Fore tribe of New Guinea died etiological agent was, unlike language which describes the of Kuru during that last 100 years. bacteria, it was resistant to early symptoms of the heat and formaldehyde disease). The southern Fore Alternative hypotheses posit treatments. people were very isolated that the infectious prions were from the rest of the world transmitted through open until the 1930s and it was scratches and wounds of the believed that they practiced a women and children who type of ritualistic cannibalism prepared the deceased victims on deceased family members. of Kuru for burial. In either This practice was linked to the case, the introduction of spread of Kuru by David modern standards for health Gadusek who studied the and sanitation have all but epidemic. eliminated Kuru in the region (with the exception of a last A puzzling finding was that known case in 2005; it is Kuru was 8-9 times more believed that Kuru can have prevalent in women and an incubation period that lasts children than in men. This in excess of 50 years). Figure 1: Hans Creutzfeldt (left) and Alfons Jakob (right) who independently first described was later attributed to the fact CJD as a distinct neurological disorder. Gadusek later won a Nobel It was not definitively known Raised awareness of TSE’s Prize for his research showing what the infectious agent of (Transmissible Spongiform that Kuru could be spread prion disease was until 1982 Encephalitis) and the prions across animal species. He when Stanley Prusiner responsible for them have took pureed brain matter from isolated and purified a single created many public health deceased Fore tribe members protein (which he called the challenges. The stability of and poured them into the prion) that could be used to these mis-folded PrP proteins cranial cavity of chimpanzees. cause infection in laboratory makes it extremely difficult to The chimpanzees developed animals. neutralize them through the symptoms similar to that of use of mild disinfectants or humans after an 18-30 month heat treatments. This means incubation period. With that prions can possibly be environmental toxins and transmitted from patient to bacterial infections ruled out patient on surgical equipment as causative agents in earlier unless careful treatment is studies, Gadusek applied to clean the hypothesized that Kuru was instruments. There are many the result of a “slow virus.” methods recommended for sterilizing instruments used to It was not until 1967 that operate on suspected CJD viruses were ruled out as the Figure 3: Stanley Prusiner patients, most involve a strong rigorously eliminated any trace of cause of prion disease. It was RNA and DNA from the chemical or enzymatic recently known that viruses, preparation of infectious disease digestion followed by a long like bacteria and eukaryotic particles. He showed for the first duration and/or high cells, used nucleic acids to time that a protein could be an temperature sterilization. transfer information and infectious agent. replicate. Therefore, it is possible to inactivate He was later awarded a Nobel infectious agents containing prize for his research which nucleic acids using certain greatly supported the wavelengths of radiation. revolutionary hypothesis that Tikvah Alper discovered that an infectious disease can the causative agent of Scrapie replicate independently from was not inactivated after long nucleic acids. In 1992, the term exposure to UV protein-only prion hypothesis radiation. These studies was given further credibility showed that the infectious when mice that had been genetically altered to knock agent was not indeed a “slow Figure 4: The first recognized case of virus” and seemed to out the PrP protein lost their Bovine Spongiform Encephalopathy (BSE), contradict the newly-formed ability to be infected with the commonly known as Mad Cow Disease central dogma of molecular Scrapie infectious agent. In was diagnosed in Britain in 1986. biology which dictates that 2005, scientists at the the replication of biological University of Texas were able agents must be mediated to artificially synthesize PrPsc Furthermore, public through the genetic coding of protein in-vitro and infect knowledge of TSE’s has been nucleic acids. hamsters that developed advanced by the media’s spongeform encephalitis. coverage of so-called “Mad incubate in humans, many Cow” outbreaks. The practice governments have imposed of rendering dead and regulations on the care and diseased animals into animal use of cattle for food. feeds, much like the However, it will take years to cannibalism hypothesis used see if they’re successful in to describe the Kuru preventing further infections. epidemic, has every now and Recent developments in then spread these prions into genetically modified healthy farm animals. organisms have led to breeds of sheep and cattle that are incapable of contracting prion Figure 6: The left image shows a cross section of a brain afflicted with Alzheimer ’s disease. A disease. Through the normal brain is on the right. Could Alzheimer’s modification of their PrP be a close relative of CJD, which is caused by protein, infectious prions are prions? The similarities are alarming. incapable of causing the conformational change necessary to propagate the Even though this research is disease. This may prove a still preliminary, it raises the viable alternative to extensive question, could Alzheimer’s sampling and testing of cattle disease be associated with Figure 5: Brain at left showing shrinkage due to prions? prion infection. for TSE’s on a routine basis and would prevent penetration ~ Christopher Massey Since prions can have a long of prions into the food supply. incubation period, many of these animals could become Recent research suggests that Alzheimer’s disease may have food products before they develop sickness. Accidental many similarities with CJD contact of meat with neural prion disease. With Here at Hardy Diagnostics, all tissue would cause prions to Alzheimer’s, the patient’s animal-based components used contaminate the meat, leading brain shrinks and degenerates in our culture media are sourced to outbreaks of BSE. Over due to the loss of neuron cells. from countries that have been 160 people in the U.K., At the University of Texas, identified by the USDA as Canada, Ireland, and the U.S.
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