Abnormal Prions Research Articles

Detection by real-time quaking-induced conversion (RT-QuIC), ELISA, and IHC of chronic wasting disease prion in lymph nodes from Pennsylvania white-tailed deer with specific PRNP genotypes

Chronic wasting disease (CWD) is a prion-mediated, transmissible disease of cervids, including deer (Odocoileus spp.), which is characterized by spongiform encephalopathy and death of the prion-infected animals. Official surveillance in the United States using immunohistochemistry (IHC) and ELISA entails the laborious collection of lymphoid and/or brainstem tissue after death. New, highly sensitive prion detection methods, such as real-time quaking-induced conversion (RT-QuIC), have shown promise in detecting abnormal prions from both antemortem and postmortem specimens. We compared RT-QuIC with ELISA and IHC for CWD detection utilizing deer retropharyngeal lymph node (RLN) tissues in a diagnostic laboratory setting. The RLNs were collected postmortem from hunter-harvested animals. RT-QuIC showed 100% sensitivity and specificity for 50 deer RLN (35 positive by both IHC and ELISA, 15 negative) included in our study. All deer were also genotyped for PRNP polymorphism. Most deer were homozygous at codons 95, 96, 116, and 226 (QQ/GG/AA/QQ genotype, with frequency 0.86), which are the codons implicated in disease susceptibility. Heterozygosity was noticed in Pennsylvania deer, albeit at a very low frequency, for codons 95GS (0.06) and 96QH (0.08), but deer with these genotypes were still found to be CWD prion-infected.

Comparative Study on Prion Protein Detection Methods Using Biosensor Technology for Beef and Its Edible Products

Prion diseases in humans are closely linked to consumption of bovine meant or organs infected with abnormal prions. Bovine organs which are most prone to prion disorders such as the brain and the liver, kidney etc are considered in various traditional cuisines over the world. Meat or edible parts should be tested safe from prions before releasing it into the market. The detection of prions proteins in bovine meat and other organs is a challenging task. The renowned methods include Quartz Crystal Microbalance and Surface Plasmon Resonance techniques. This paper narrates a performance analysis of the accuracy, sensitivity and feasibility of each technique over the other for the detection of abnormal prion protein. Successful detection of the infected prions will reduce the diseases related to abnormal prions in entering the food chain.

Chronic wasting disease of deer – is the battle to keep Europe free already lost?

CHRONIC wasting disease (CWD) is a prion disease affecting many species of deer, which was, until recently, confined to North America. However, confirmed diagnoses in Norway in both reindeer (...

Beef from the United States: Is It Safe?

Beef from the United States: Is It Safe?

Manifestaciones psiquiátricas por priones. Una revisión narrativa

Prion diseases are a group of rare and rapidly progressive neurodegenerative conditions that may cause neuropsychiatric symptoms. This group of diseases has been described since the 18th century, but they were recognized decades later, when it became clear that the humans were affected by infected animals. There was controversy when the problem was attributed to a single protein with infective capacity. The common pathological process is characterized by the conversion of the normal cellular prion protein into an abnormal form. In humans, the illness has been classified as idiopathic, inherited and acquired through exposure to exogenous material containing abnormal prions. The most prominent neurological manifestation of prion diseases is the emergence of a rapidly progressive dementia, mioclonus associated with cerebellar ataxia and also extra pyramidal symptoms. Psychiatric symptoms occur in early stages of the illness and can contribute to timely diagnosis of this syndrome. Psychiatric symptoms have traditionally been grouped in three categories: affective symptoms, impaired motor function and psychotic symptoms. Such events usually occur during the prodromal period prior to the neurological manifestations and consists in the presence of social isolation, onset of delusions, irritability/aggression, visual hallucinations, anxiety and depression, and less frequent first-rank symptoms among others. Definite diagnosis requires post mortem examination. The possibility that a large number of cases may occur in the next years or that many cases have not been considered with this diagnosis is a fact.In our opinion, psychiatrists should be aware of symptoms of this disease. The main objective of this research consisted of assessing the correlation between this disturbance and neuro-psychiatric symptoms and particularly if this psychiatric manifestations integrate a clinical picture suggestive for the diagnosis of these diseases, but firstly reviewed taxonomic, pathogenic and pathological aspects. The authors of this project also added an element in relation to some diagnostic considerations based on scientific evidence. For the search controlled descriptors applied to the research for indexing scientific articles in databases were used. The electronic data bases used were PubMed, EMBASE and also PsycInfo. The descriptors were prion diseases, psychotic disorders, depression, mood disorders, pathology, classification, prion protein, history, neurological manifestations, and psychiatric manifestations. The selection criteria for the material were qualitative. To conclude, and based on the extensive literature review, the authors propose that the period where the evidence is more robust for mental impaired is named “psychiatric symptoms phase, which can be extended for a few months, being the psychiatric affective symptoms the most characteristic of this phase. In conclusion, we considered that the identification of these symptoms in a patient with risk factors for developing the disease will contribute to the early identification, and would regulate the guidelines in suspected diagnosis of this group of disorders. The intention is provide a better quality of life to the sick people.

Development of dose-response models of Creutzfeldt-Jakob disease infection in nonhuman primates for assessing the risk of transfusion-transmitted variant Creutzfeldt-Jakob disease.

Estimates for the risk of transmitting variant Creutzfeldt-Jakob disease (vCJD) via blood transfusion have relied largely on data from rodent experiments, but the relationship between dose (amount of infected blood) and response (vCJD infection) has never been well quantified. The goal of this study was to develop a dose-response model based on nonhuman primate data to better estimate the likelihood of transfusion-transmitted vCJD (TTvCJD) in humans. Our model used dose-response data from nonhuman primates inoculated intracerebrally (i.c.) with brain tissues of patients with sporadic and familial CJD. We analyzed the data statistically by using a beta-Poisson dose-response model. We further adjusted model parameters to account for the differences in infectivity between blood and brain tissue and in transmission efficiency between intravenous (i.v.) and i.c. routes to estimate dose-dependent TTvCJD infection. The model estimates a mean infection rate of 76% among recipients who receive one unit of whole blood collected from an infected donor near the end of the incubation period. The nonhuman primate model provides estimates that are more consistent with those derived from a risk analysis of transfused nonleukoreduced red blood cells in the United Kingdom than prior estimates based on rodent models. TTvCJD was recently identified as one of three emerging infectious diseases posing the greatest immediate threat to the safety of the blood supply. Cases of TTvCJD were reported in recipients of nonleukoreduced red blood cells and coagulation factor VIII manufactured from blood of United Kingdom donors. As the quantity of abnormal prions (the causative agent of TTvCJD) varies significantly in different blood components and products, it is necessary to quantify the dose-response relationship for a wide range of doses for the vCJD agent in transfused blood and plasma derivatives. In this paper, we suggest the first mechanistic dose-response model for TTvCJD infection based on data from experiments with nonhuman primates. This new model may improve estimates of the possible risk to humans.

The Extinction of Homo Sapiens and Symbiotic Neanderthalisation: Relation to Archaeal Mediated RNA Viroidsand Amyloidosis

Introduction: Prion proteins have been implicated in systemic disorders like neurodegenerations, cancer and metabolic syndrome. The beta amyloid in Alzheimer’s disease, alpha synuclein in parkinson’s disease, the TAR protein in frontotemporal dementia and copper zinc dismutase in motor neuron disease behaves like prion proteins. Prion proteins like behavior is also seen in the tumour suppressor P53 protein in cancer and the islet cell associated amyloid in diabetes mellitus. Prion diseases are conformational diseases. The abnormal prion protein seeded into the system converts the normal proteins with prion like domains to abnormal configuration. This abnormal protein resists digestion by lysosomal enzymes after its half-life is over and results in deposition of amyloid plaques. This produces organ dysfunction. Prion phenomena were initially described for Creutzfeldt Jakob’s disease, but now it is found to be wide spread in chronic disease pathogenesis. Ribonucleoproteins are well known to behave like prion proteins and form amyloid. We have demonstrated actinidic archaea which secretes RNA viroids in metabolic syndrome, neurodegenerations, cancer, autoimmune disease, schizophrenia, autism and CJD. The RNA viroids can bind with normal proteins with prion like domains eg., superoxide dismutase and produce a ribonucleoprotein resulting in prion phenomena and amyloidogenesis. Materials and Methods: The following groups were included in the study:- alzheimer’s disease, multiple sclerosis, non-hodgkin’s lymphoma, metabolic syndrome x with cerebrovascular thrombosis and coronary artery disease, schizophrenia, autism, seizure disorder, creutzfeldt jakob disease and acquired immunodeficiency syndrome. There were 10 patients in each group and each patient had an age and sex matched healthy control selected randomly from the general population. The blood samples were drawn in the fasting state before treatment was initiated. Plasma from fasting heparinised blood was used and the experimental protocol was as follows (I) Plasma+phosphate buffered saline, (II) same as I+cholesterol substrate, (III) same as II+cerium 0.1 mg/ml, (IV) same as II+ciprofloxacine and doxycycline each in a concentration of 1 mg/ml. Cholesterol substrate was prepared as described by Richmond. Aliquots were withdrawn at zero time immediately after mixing and after incubation at 37oC for 1 hour. The following estimations were carried out:- Cytochrome F420, free RNA, Cytochrome F420 was estimated flourimetrically (excitation wavelength 420 nm and emission wavelength 520 nm). Results: Plasma of control subjects showed increased levels of the above mentioned parameters with after incubation for 1 hour and addition of cholesterol substrate resulted in still further significant increase in these parameters. The plasma of patients showed similar results but the extent of increase was more. The addition of antibiotics to the control plasma caused a decrease in all the parameters while addition of cerium increased their levels. The addition of antibiotics to the patient’s plasma caused a decrease in all the parameters while addition of cerium increased their levels but the extent of change was more in patient’s sera as compared to controls. Discussion: The actinidic archaeal growth results in increased digoxin synthesis and phenotypic conversion of homo sapiens to homo Neanderthals as reported earlier. The increased actinidic archaeal growth is due to global warming and these results in neanderthalisation.Homo neanderthalis tend to have more of civilisational diseases like metabolic syndrome, neurodegenerations, cancer, autoimmune disease, schizophrenia, autism and CJD. Actinidic archaeal secreted RNA viroids may play a crucial role in amyloid formation and pathogenesis of these disorders. The evolution and origin of homo sapiens and homo neanderthalis is on the basis of actinidic archaeal symbiosis and digoxin synthesis. Extreme climate change related increased actinidic archaeal symbiosis and digoxin synthesis results in homo neanderthalis. The homo sapien species results from inhibition of actinidic archaeal symbiosis and endogenous digoxin synthesis by normal global climate. Thus there are evolutionary swings between the two human species depending on extremes of climate and archaeal symbiosis. Endogenous digoxin can be considered as a Neanderthal hormone. The results show that there was increase in cytochrome F420 in CJD and other disease groups indicating increased archaeal growth. There was also an increase in free RNA indicating self-replicating RNA viroids in CJD and other disease groups. The RNA viroid generation was catalysed by actinides. The RNA viroids can bind with proteins having prion like domains forming ribonucleoproteins. These ribonucleoproteins can give an abnormal conformation to the protein resulting in generation of abnormal prions. The abnormal prions can act as a template to convert normal proteins with normal configuration to abnormal conformation. This can result in amyloidogenesis. The abnormal configured proteins will resist lysosomal digestion and accumulate as amyloid producing disease states and extinction.

Hazardous Effect Free From Decontamination

Adventitious agents are those that are not inherent in the production of biopharmaceuticals. Microbial adventitious agents, Microbiocidal agents, help for inactivation of viruses, bacteria, fungi, mycoplasma, bacterial spore and sometimes prion. Bovine spongiform encephalopathy (BSE) agents, abnormal prions, are also potential adventitious agents. Adventitious agents can be introduced during establishment of cell lines, cell culture/fermentation, capture and downstream processing steps, formulation/filling, and even during drug delivery Therapeutic biotechnology products must have excellent safety characteristics. However, the potential introduction of adventitious agents must continually be evaluated for safety. The testing procedures that is performed for this purpose is addressed in regulatory documents that include ICH guidelines, European U.S., and Japanese Pharmacopoeia (EP,USP and JP) documents. In some cases, 9 CFR (U.S. Code of Federal Regulations) and 21 CFR, 211 and 610 are also applicable.

Cryopreservative solution using rakkyo fructan as cryoprotectant

Cryopreservation of the cells allows great flexible application for cell therapy, as well as industrial production of biologics such as antibody therapeutics. Conventionally, cryopreservative solution contains both of fetal bovine serum (FBS) and dimethyl sulfoxide (DMSO) as a cryoprotectant [1]. However, both of them have problems. FBS frequently induces differentiation of stem cells and so it should not be used for cell therapy. Additionally, FBS has serious concern about zoonotic infections such as abnormal prions, pathogen of bovine spongiform encephalopathy (BSE) [2,3], indicating necessity of FBS-free cryopreservative solution. DMSO has cytotoxicity and often induces stem cells to differentiate [3]. Therefore, it is necessary to reduce the concentration of DMSO in cryoprotectant solution. In this study, we report that rakkyo fructan, plant-derived polysaccharide, significantly improved the viability of the cells frozen in DMSO-free solution.

Consumption of Bovine Spongiform Encephalopathy (BSE) Contaminated Beef and the Risk of Variant Creutzfeldt‐Jakob Disease

To date, the variant Creutzfeldt-Jakob disease (vCJD) risk assessments that have been performed have primarily focused on predicting future vCJD cases in the United Kingdom, which underwent a bovine spongiform encephalopathy (BSE) epidemic between 1980 and 1996. Surveillance of potential BSE cases was also used to assess vCJD risk, especially in other BSE-prevalent EU countries. However, little is known about the vCJD risk for uninfected individuals who accidentally consume BSE-contaminated meat products in or imported from a country with prevalent BSE. In this article, taking into account the biological mechanism of abnormal prion PrP(res) aggregation in the brain, the probability of exposure, and the expected amount of ingested infectivity, we establish a stochastic mean exponential growth model of lifetime exposure through dietary intake. Given the findings that BSE agents behave similarly in humans and macaques, we obtained parameter estimates from experimental macaque data. We then estimated the accumulation of abnormal prions to assess lifetime risk of developing clinical signs of vCJD. Based on the observed number of vCJD cases and the estimated number of exposed individuals during the BSE epidemic period from 1980 to 1996 in the United Kingdom, an exposure threshold hypothesis is proposed. Given the age-specific risk of infection, the hypothesis explains the observations very well from an extreme-value distribution fitting of the estimated BSE infectivity exposure. The current BSE statistics in the United Kingdom are provided as an example.

The prion dilemma confounding science educators

In this paper, the issue of the prion hypothesis, a simmering controversy within the scientific community, is addressed. We inquire into the appropriateness of the use of certain augmentations and rhetoric approaches used during scientific debates, as well as the aptness of unequivocal statements in textbooks that indicate “abnormal prions” as a primary cause of Transmissible Spongiform Encephalopathies.

The prion dilemma confounding science educators

In this paper, the issue of the prion hypothesis, a simmering controversy within the scientific community, is addressed. We inquire into the appropriateness of the use of certain augmentations and rhetoric approaches used during scientific debates, as well as the aptness of unequivocal statements in textbooks that indicate “abnormal prions” as a primary cause of Transmissible Spongiform Encephalopathies.

Mechanism of peptide modification by low-temperature microwave plasma

The possibility of changing the biological function of peptides was investigated using low pressure microwave plasma, aiming to develop a new and efficient technique to inactivate biohazardous proteinaceous molecules such as abnormal prions and figure out the insights of the interactions between non-reactive plasmas and peptide molecules. In the present research, a peptide, Arginine Vasotocin, having an inherent bio-function of controlling the water penetrability through amphibian abdominal skin was used. The interaction with low temperature plasma is investigated. The mechanisms involved in the modifications produced by argon plasma exposure are discussed, according to the obtained results of X-ray photoelectron spectroscopy, mass spectrometry, nuclear magnetic resonance, and water penetrability tests. The loss of water enhancement property of the peptide molecules after argon plasma treatment is explained.

In Vitro Microbial Degradation of Abnormal Prions in Central Nervous System from Scrapie Affected Sheep

Abnormal prion protein (PrP Sc ) is highly resistant to inactivation by conventional chemical and physical means. This study was to determine if microbes from the environment could be used to degrade PrP Sc in central nervous system (CNS) tissues from scrapie positive sheep as measured by Western blot. In the first experiment, the number of microbes in CNS tissue suspended in saline was reduced by autoclaving the suspension at 121°C for 5 minutes. Aliquots of this preparation were then inoculated with additional ovine fecal microbes and controls were not inoculated. The results showed that the addition of microbes increased the degradation of PrP Sc in specimens during incubation at room temperature (RT) or at 60°C, but the reduction was greatest at 60°C. In the second experiment, a separate tissue suspension in saline was prepared from CNS tissue from each of 4 scrapie positive sheep and from each of 4 negative sheep. All specimens contained bacteria and after 90 days of incubation at 60°C, PrP Sc in CNS specimens was degraded beyond the detection limit in tissues from 2 scrapie positive sheep and was partially degraded in the other two specimens. The tissues from scrapie negative sheep were consistently negative for PrP Sc . Analysis of microbial 16S ribosomal DNA indicated that during the 90 day incubation period the microbe population shifted from a predominance of mesophiles to thermophiles, based on guanine-cytosine (GC) content of ribosomal RNA genes. The results in this study suggest that microbes commonly found in sheep carcasses or manure could play a role in the degradation of PrP Sc in CNS tissues during incubation at 60°C.

Prions: Introducing a Complex Scientific Controversy to a Biology Classroom

Research Article| November 01 2009 Prions: Introducing a Complex Scientific Controversy to a Biology Classroom Igor V. Zaitsev Igor V. Zaitsev Search for other works by this author on: This Site PubMed Google Scholar The American Biology Teacher (2009) 71 (9): 525–530. https://doi.org/10.2307/20565374 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Igor V. Zaitsev; Prions: Introducing a Complex Scientific Controversy to a Biology Classroom. The American Biology Teacher 1 November 2009; 71 (9): 525–530. doi: https://doi.org/10.2307/20565374 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu nav search search input Search input auto suggest search filter All ContentThe American Biology Teacher Search This content is only available via PDF. Copyright National Association of Biology Teachers Article PDF first page preview Close Modal You do not currently have access to this content.

Prions: Introducing a Complex Scientific Controversy to a Biology Classroom

[ILLUSTRATION OMITTED] It has been almost 50 years since Thomas Kuhn, in The Structure of Scientific Revolutions, posited that science does not progress by steady accumulation of knowledge, but rather by a system of competition among paradigms. They vie for supremacy through greater parsimony, explanatory power, and popularity among community of scientists (Kuhn, 1962). The current controversy concerning identity of (PrPs) (proteins devoid of nucleic acid) as infectious agents of transmissible spongiform encephalopathies (TSE) elucidates all issues involved in just such a debate. While modern biology high school and university textbooks cover many scientific controversies that have been resolved decades and even centuries ago, they fail to cover current scientific disputes. This article is intended to address such an omission by introducing prion controversy in biology classes in high schools and colleges. In 1982, biochemist and neurologist Stanley Prusiner proposed a hypothesis concerning infectious proteins. He identified them as abnormal prions, proteinaceous infectious particles capable of converting normal (naturally present proteins in mammals) into an abnormal form causing a fatal disease of central nervous system (CNS) in both animals and humans. Heretofore, it had been accepted that infections could be caused only by protozoans, fungi, bacteria, rickettsia, viruses, or viroids. Only nucleic acids, informational polymers, were known to be able to duplicate themselves, not proteins. For discovery of which Prusiner posited can cause TSE, he received a Nobel Prize in 1997. Were Prusiner's hypothesis correct, our understanding of organic world would be changed forever. However, Laura Manuelidis (2007), one of most dedicated scientists in this field and head of neuropathology at Yale School of Medicine, contends that prions thereby became canonized, although careful review of data revealed many discrepancies. Indeed, even Nobel Prize winners can err (Allchin, 2008), including Prusiner, and thus remain in realm of a hypothesis (Manuelidis, 2007). Despite overwhelming opposing data published in The Lancet, Science, Virology, The Journal of Virology, Journal of Cellular Biochemistry, Viral Immunology, Journal of NeuroVirology, Proceedings of National Academy of Sciences, and many other scientificpublications, most, if not all, biology textbooks in U.S. present asthe primary cause of TSE. While there are scientists convinced of ability of abnormal to cause infections, there are other scientists who, based on their observations and experimental data, do not think that could become infectious. Manuelidis suggests that may simply be part of late stage of a disease, not part of cause (Mihailova, 2007), and PrP infectivity is questionable, and perhaps non-existent (Manuelidis, 2007). * Cannibalism & Rise of TSE Since students seem more engaged when instructors incorporate examples from popular culture into classroom discussions (Pryor, 2008), one might start a consideration of with mention of Kurt Vonnegut's science fiction novel, Cat's Cradle (1963), before introducing Deadly Feasts (1997), a shocking nonfiction case history of discovery and epidemiology of fatal disease TSE. Certainly, truth is stranger than fiction if one were to contrast Richard Rhodes' documented study and any of Vonnegut's science fiction novels. Cat's Cradle, concluding in an apocalyptic climax, concerns ability of a nucleant that can turn water into ice, just as an abnormal prion can allegedly turn its host into abnormal forms, resulting in this fatal brain pathology. Deadly Feasts begins with a description of a burial ceremony that women of Fore tribe used to practice in New Guinea, the last wild place on earth. Sixty or more native women with their babies and small children, family of a deceased woman, would gather to bury her in their stomachs rather than abandon her to rot in ground. …

The In Vitro Bioassay Systems for the Amplification and Detection of Abnormal Prion PrPSc in Blood and Tissues

Prion diseases or transmissible spongiform encephalopathies, including Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD), are chronic neurodegenerative diseases characterized by accumulation of abnormal infectious prions known as PrPSc. Infectious prion is emerging as a blood transfusion-transmissible pathogen and is present at extremely low levels in the blood of asymptomatic patients, which is not detectable by current standard methodologies. As such, prion-related diseases impose a huge challenge to blood transfusion services around the world. Rapid, sensitive, and specific assays are thus urgently needed to detect trace amounts of infectious prions in the blood or tissues of asymptomatic patients, as early diagnostic blood transfusion and screening tools. Recent advances in the in vitro assay technologies including protein misfolding cyclic amplification and immunoassays have made it possible to detect infectious prions in the blood of animals with scrapie and even of asymptomatic animals infected with prions. These assays thus bring some hope for the possibility of detecting infectious prions in human blood and tissues for both early diagnosis for blood transfusion and transplantation screening purposes. This review focuses on the development of the various in vitro bioassay systems for the rapid amplification and detection of infectious prions that might be present in blood and tissues for blood transfusion and transplantation recipients.

Age-dependent increase of clusterin in the human pituitary gland

Clusterin is a glycoprotein known to play various physiological roles including complement activity, amyloid binding activity in Alzheimer disease, as well as binding with heat shock proteins and abnormal prions. The present study immunohistochemically investigated the expression of clusterin in the human pituitary gland in subjects of 10–88 years of age ( n=173). Causes of death were blunt injury ( n=35), sharp injury ( n=15), poisoning ( n=11), drowning ( n=14), fire fatalities ( n=28), asphyxiation ( n=15), hypothermia ( n=7), hyperthermia ( n=3), and natural diseases ( n=45). Clusterin was detected in mixed cell follicles and the anterior lobar parenchymal cells. The area occupied by cells positive for clusterin were measured, and the ratio to the whole area of the anterior lobe (% clusterin-positive cell area) was estimated. There was a good correlation between the age of the subjects in years and the % clusterin-positive cell area in the anterior lobe of the pituitary gland ( r=0.736, P<0.01). Relationships between % clusterin-positive cell and gender, cause of death, and survival time were insignificant. These findings indicate an age-dependent accumulation of clusterin in the pituitary gland, which may be related to the aging of endocrine systems.

Editors Note

Prion diseases are a group of rare and uniformly fatal neurodegenerative disorders in humans and animals.These diseases are characterized by spongiform changes within the central nervous system. In recent years,much attention has been focused on prion diseases in animals, which include bovine spongiformencephalopathy, scrapie in sheep; transmissible encephalopathy in the mink and chronic wasting disease indeer, elk and mule. The human counterpart of prion diseases include classic Creutzfeldt-Jakob disease, (CJD)and varient CJD (vCJD), Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, kuru and Alperssyndrome.While the molecular mechanism(s) of prion diseases is actively investigated, it is currently believed thatinfectious prion proteins are misfolded in such a way that they can create a series of changes leading to thetransformation of normal prion proteins into abnormal ones in a self-propagating manner. The ultimate result ofaccumulation of abnormal prions result in neuronal death and degeneration.The recent discovery of BSE, or “mad cow” disease in England and in the US has raised many concernsrelated to the consumption of beef. Medical care givers are trying to determine how to educate their patientsso that they understand the legitimate health risks and differentiate them from the abundance of myths.Clearly, much research is needed before every aspect of these diseases will be sorted out.In this special issue of Current Molecular Medicine we have put together review articles from some of theacknowledged leaders in the field of prion research in addition to our regularly scheduled review articles. Wehope that our efforts serve the readers in gaining better understanding of the biology and molecularmechanisms and stimulate further research in this important area of investigation.

Molecular Pathology of Prions

Edited by Harry F. Baker, Humana PressMolecular Pathology of Prions is multiauthored text that describes the recent advances in the molecular biology of prion disorders. The major goal of the book is to address the pathologic mechanisms leading to the generation of spongiform encephalopathies. This is a timely topic, not only for the fact that Stanley Prusiner and Carleton Gajdusek recently won the Nobel Prize for their work on prions, but also because of the emergence of the new variant of Creutzfeldt-Jakob disease as a result of bovine spongiform encephalopathy in Great Britain. Although the book is part of a Methods in Molecular Medicine series, the editor has specifically not used the cookbook method format that was used in a previous edition in 1996. Instead, the editor has assembled a cross-section of work by some of the leading researchers in the field and, to use his own words, “I have concentrated on the molecular pathogenesis of prion disease and the emphasis is on the role of the prion protein. There is no mention of the epidemiology of animal and human prion diseases that figured so prominently in the earlier book.” Therefore, the major purpose is to have the authors discuss how their research is addressing some of the unanswered questions regarding the biology of the prion protein.The book has 14 chapters, which are preceded by a well-done philosophical overview by Rosalind M. Ridley about how novel hypotheses, of which the prion hypothesis certainly was one, evolve into scientific fact. The next 2 chapters, by Kretzschmar et al and David R. Brown and Ian M. Jones, respectively, discuss proposed functions of the normal prion protein. Chapter 4, by David R. Brown, describes immunohistochemical analysis of the abnormal prion proteins in bovine spongiform encephalopathy and scrapie. Chapter 6, by Stephen J. DeArmond, gives a very interesting discussion about the differential targeting of neurons by different prion strains. The next chapter, by Glenn C. Telling, describes transgenic animal studies of prion diseases. In this chapter, he details research showing that knock-out animals for the normal prion protein are not able to develop spongiform encephalopathies when inoculated. This finding supports the prion-only hypothesis of prion replication. Chapter 8, by Glatzel et al, is entitled “Prions: From Neurografts to Neuroinvasion.” Chapter 9, by Harris et al, describes work on familial prion diseases in transgenic animals. Chapter 10, by Samar Betmouni and V. Hugh Perry, discusses the role of inflammation in the pathogenesis of prion disease. This had been a previously understudied area, and the authors give a very lucid account of how prion amyloid deposition may in fact be an inflammatory response. In the next chapter, J. Richard Green describes experiments on the electrophysiologic effects of abnormal prions in neuronal cells. Chapter 12, by Martin Jeffery and Jan R. Fraser, presents evidence that there is extracellular conversion of the prion proteins that is typical of classic amyloidosis. The next chapter, by Wisniewski et al, is a very interesting discussion of their work aimed at developing therapeutic agents composed of conformational isoforms of both prions and amyloid-β to block amyloid deposition not only in spongiform encephalopathies, but also in Alzheimer disease. Finally, the last, very provocative chapter, by Wicker et al, describes how prions in yeast may be proteins that mediate inheritance.Overall, the editor has put together work by some of the leading prion researchers that helps clarify the more recent advances in the field. This book would most likely appeal to someone who has a basic working knowledge of prion diseases. Therefore, it would be an excellent addition to the libraries of neuropathologists, neurologists, or molecular neuroscientists. However, it would also be a good resource for and give valuable insights to any of those individuals who are studying the molecular mechanisms of amyloidosis in general.