The Misfolded Protein
RSShahaha “Remember, there is no spoon” another video about Prions
This is an interesting video that I found wandering by Vimeo, from The ISU Institute of Rural Health, enjoy it!
One Student Against the World: Mad Cow Disease. Could You be a Carrier?
Prion diseases such as bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) are able to jump species much more easily than previously thought. A study published in Science today shows that in mice, prions introduced from other species can replicate in the spleen…
(Source: scientificamerican.com)
A prion is an infectious agent composed of protein in a misfolded form. This is in contrast to all other known infectious agents, which must contain nucleic acids (either DNA, RNA, or both). The word prion, coined in 1982 by Stanley B. Prusiner, is aportmanteau derived from the words protein and infection. Prions are responsible for the transmissible spongiform encephalopathies in a variety of mammals, including bovine spongiform encephalopathy (BSE, also known as “mad cow disease”) in cattle and Creutzfeldt–Jakob disease (CJD) in humans. All known prion diseases affect the structure of the brain or other neural tissue and all are currently untreatable and universally fatal.
In Search Of Misfolded Proteins
“The researchers have already used the technique to detect misfolded protein aggregates in cerebrospinal fluid from Alzheimer’s patients (PLoS One, DOI:10.1371/journal.pone.0015725). They now plan to test the diagnostic usefulness of the assay in larger groups of patients with Alzheimer’s and other diseases.”
The Prion Diseases_Stanley B. Prusiner
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[…]Prions, once dismissed as an impossibility, have now gained wide recognition as extraordinary agents that cause a number of infectious, genetic and spontaneous disorders
by Stanley B. Prusiner.[…]
Prions_Stanley B. Prusiner
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[…]ABSTRACT Prions are unprecedented infectious pathogens that cause a group of invariably fatal neurodegenerative diseases by an entirely novel mechanism. Prion diseases may present as genetic, infectious, or sporadic disorders, all of which involve modification of the prion protein (PrP). Bovine spongiform encephalopathy (BSE), scrapie of sheep, and Creutzfeldt–Jakob disease (CJD) of humans are among the most notable prion diseases. Prions are transmissible particles that are devoid of nucleic acid and seem to be composed exclusively of a modified protein (PrPSc). The normal, cellular PrP (PrPC) is converted into PrPSc through a posttranslational process during which it acquires a high b-sheet content. The species of a particular prion is encoded by the sequence of the chromosomal PrP gene of the mammals in which it last replicated. In contrast to pathogens carrying a nucleic acid genome, prions appear to encipher strain-specific properties in the tertiary structure of PrPSc. Transgenetic studies argue that PrPSc acts as a template upon which PrPC is refolded into a nascent PrPSc molecule through a process facilitated by another protein. Miniprions generated in transgenic mice expressing PrP, in which nearly half of the residues were deleted, exhibit unique biological properties and should facilitate structural studies of PrPSc. While knowledge about prions has profound implications for studies of the structural plasticity of proteins, investigations of prion diseases suggest that new strategies for the prevention and treatment of these disorders may also find application in the more common degenerative diseases.[…]
Molecule of the month: Prions_RCSB_Protein DataBase
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[…]Prions are proteins that can adopt two different forms, a normal form and a misfolded form. This may not seem unusual, since many proteins are flexible and adopt different shapes. However, prions have another unusual characteristic: the misfolded form of the prion can force normal prions to change into the misfolded shape. In this way, a few misfolded prions can corrupt a whole population of normal prions, converting them one-byone into the misfolded shape. This can have deadly consequences, as the levels of misfolded proteins build up. For instance, misfolding of the PrP prion causes fatal neural diseases in humans and other mammals. To make things worse, misfolded prions are infectious, so a small dose of misfolded prions can infect and corrupt an entire organism.[…]
Prion species barrier batween the closely related yeast proteins is detected despite coaggregation
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[…]Prions are self-perpetuating and, in most cases, aggregation-prone protein isoforms that transmit neurodegenerative diseases in mammals and control heritable traits in yeast. Prion conversion requires a very high level of identity of the interacting protein sequences. Decreased transmission of the prion state between divergent proteins is termed ‘‘species barrier’’ and was thought to occur because of the inability of divergent prion proteins to coaggregate. Species barrier can be overcome in cross-species infections, e.g., from ‘‘mad cows’’ to humans. We studied the counterparts of yeast prion protein Sup35, originated from three different species of the Saccharomyces sensu stricto group and exhibiting the range of prion domain divergence that overlaps with the range of divergence observed among distant mammalian species. All three proteins were capable of forming a prion in Saccharomyces cerevisiae, although prions formed by heterologous proteins were usually less stable than the endogenous S. cerevisiae prion. Heterologous Sup35 proteins coaggregated in the S. cerevisiae cells. However, in vivo cross-species prion conversion was decreased and in vitro polymerization was cross-inhibited in at least some heterologous combinations, thus demonstrating the existence of prion species barrier. Moreover, the barrier between the S. cerevisiae protein and its Saccharomyces paradoxus and Saccharomyces bayanus counterparts was asymmetric both in vivo and in vitro. Our data show that a decreased cross-species prion transmission does not necessarily correlate with a lack of crossspecies coaggregation, suggesting that species-specificity of prion transmission is controlled at the level of conformational transition rather than coaggregation.[…]
Prions of Fungi Inherited Structures and Biological Roles
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[…]The term ‘prion’ means an infectious protein that does not need an accompanying nucleic acid. There are six fungal prions, including four self-propagating amyloids and two enzymes that are necessary to activate their inactive precursors. Here we explore the scope of the prion phenomenon, the biological and evolutionary roles of prions, the structural basis of the amyloid prions, and the prominent role of chaperones (proteins that affect the folding of other proteins) and other cellular components in prion generation and propagation.[…]
Research Suggests Alternate Course of Prion Infections
Prion diseases are contagious spongiform encephalopathies (read: your brain turns into a sponge over time) caused by prions, or misfolded proteins. You’ve heard of prion diseases like Mad Cow Disease in cows, Scrapie in sheep, and Creutzfeldt–Jakob disease in humans. Prion diseases are unlike all others, becuase they progress as the misfolded proteins induce normal proteins to misfold into prions themselves, which then misfold other proteins, etc. The culprit protein was isolated as recently 1982, so the diseases are poorly understood. Since their discovery, the leading hypothesis about prion disease is that they progress as a slow, gradual buildup of prions. As all of the healthy proteins are destroyed, so says the theory, a critical mass is reached, leading to neurodegeneration and death.
That’s not the case, according to new research conducted in London. Scientists at the UK Medical Research Council Prion Unit found that, in mice, prions build up quickly and then stop. Once a ceiling of about 100 million prion particles per brain is reached, the level of prions apparently stabilizes, without manifesting in any symptoms of the disease. The prion count doesn’t appear to be in equilibrium; if healthy proteins are added to a sick brain, the level of prions doesn’t increase. Scientists now believe that some unknown catalyst launches a second phase of the disease, announced by the symptoms commonly associated with prions. And, just to complicate matters, the delay between buildup and disease was lengthened when more healthy proteins were added to the brain.
As the research is very new, we don’t yet know if the updated hypothesis will withstand the test of time. Even still, it is an interesting twist in the narrative of an already fascinating disease.
[Full disclose: my uncle does research on prion diseases at the University of Montana-Bozeman, so I’m predisposed to thinking they’re awesome.]
Prion Diseases_Richard T Johnson
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[…]Prion diseases are degenerative disorders of the nervous system caused by transmissible particles that contain a pathogenic isoform of the prion protein, a normal constituent of cell membranes. The most common human prion disease is Creutzfeldt-Jakob disease (CJD). Most cases are sporadic with unknown mode of transmission, 10–15% of cases are inherited, and a small number have been transmitted by medical procedures. The spread of human prion diseases through consumption of infected material has been implicated historically in kuru and recently in variant CJD. Animal prion diseases (scrapie of sheep, transmissible mink encephalopathy, chronic wasting disease of cervids, and bovine spongiform encephalopathy) all seem to be laterally transmitted by contact with infected animals or by consumption of infected feed. The different modes of transmission of different prion diseases, the unpredictable species barriers, the variable distribution of infectivity in tissues, and strain variations found in some diseases all make risk assessment and predictions of future events difficult.[…]
Prion Diseases Guide to Surveillance, Reporting and Control: Massachusetts Department of Public Health
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[…] A. Etiologic Agent Prion diseases, also known as transmissible spongiform encephalopathies (TSE), are a group of rare, rapidly progressive, and fatal neurologic diseases. The agents responsible for human and animal prion diseases are thought to be abnormal proteins (protease-resistant prion protein, or PrP-res) that can trigger chain reactions causing normal proteins in the brain to change to the abnormal protein. These abnormal proteins are resistant to enzymatic breakdown, and they accumulate in the brain, leading to damage. There are a number of animal and human prion diseases. Human diseases include Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker Disease (GSS), fatal familial insomnia (FFI), kuru, and variant CJD (vCJD). CJD has several sub-categories: sporadic (sCJD, accounting for 80–90% of CJD cases); familial (hereditary CJD); iatrogenic (associated with treatment and transplant, such as use of infected dura mater patches or administration of human pituitary-derived hormones); and variant (vCJD, associated with exposure to bovine spongiform encephalopathy [BSE]). Examples of animal prion diseases include scrapie in sheep and goats, chronic wasting disease (CWD) in deer and elk, transmissible mink encephalopathy (TME), feline spongiform encephalopathy, and BSE (also called “mad cow disease”).[…]
Prion-like transmission of protein aggregates in neurodegenerative diseases
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[…]Neurodegenerative diseases are commonly associated with the accumulation of intracellular or extracellular protein aggregates. Recent studies suggest that these aggregates are capable of crossing cellular membranes and can directly contribute to the propagation of neurodegenerative disease pathogenesis. We propose that, once initiated, neuropathological changes might spread in a ‘prionlike’ manner and that disease progression is associated with the intercellular transfer of pathogenic proteins. The transfer of naked infectious particles between cells could therefore be a target for new disease-modifying therapies.[…]
Le Prion_un Agent Pathogène encore Mystèrieux.
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[…]LE PRION :
UN AGENT PATHOGÈNE ENCORE MYSTÉRIEUX
• une protéine que nous possédons tous pourrait
devenir destructrice lorsqu’elle change de forme
• plusieurs axes de recherche à l’Institut Pasteur
portent sur la protéine PrP et sur le prion […]
About The Misfolded Protein
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