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Open AccessArticle Evaluation of the Zoonotic Potential of Transmissible Mink Encephalopathy

by Emmanuel E. Comoy, Jacqueline Mikol, Marie-Madeleine Ruchoux, Valérie Durand, Sophie Luccantoni-Freire, Capucine Dehen, Evelyne Correia, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Juan Maria Torres, Paul Brown and Jean-Philippe Deslys

Pathogens 2013, 2(3), 520-532; doi:10.3390/pathogens2030520

Received: 27 June 2013 / Revised: 28 July 2013 / Accepted: 30 July 2013 / Published: 30 July 2013

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Abstract

Successful transmission of Transmissible Mink Encephalopathy (TME) to cattle supports the bovine hypothesis for the still controversial origin of TME outbreaks. Human and primate susceptibility to classical Bovine Spongiform Encephalopathy (c-BSE) and the transmissibility of L-type BSE to macaques indicate a low cattle-to-primate

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Successful transmission of Transmissible Mink Encephalopathy (TME) to cattle supports the bovine hypothesis for the still controversial origin of TME outbreaks. Human and primate susceptibility to classical Bovine Spongiform Encephalopathy (c-BSE) and the transmissibility of L-type BSE to macaques indicate a low cattle-to-primate species barrier. We therefore evaluated the zoonotic potential of cattle-adapted TME. In less than two years, this strain induced in cynomolgus macaques a neurological disease similar to L-BSE but distinct from c-BSE. TME derived from another donor species (raccoon) induced a similar disease with even shorter incubation periods. L-BSE and cattle-adapted TME were also transmissible to transgenic mice expressing human prion protein (PrP). Secondary transmissions to transgenic mice expressing bovine PrP maintained the features of the three tested bovine strains (cattle TME, c-BSE and L-BSE) regardless of intermediate host. Thus, TME is the third animal prion strain transmissible to both macaques and humanized transgenic mice, suggesting zoonotic potentials that should be considered in the risk analysis of animal prion diseases for human health. Moreover, the similarities between TME and L-BSE are highly suggestive of a link between these strains, and therefore the possible presence of L-BSE for many decades prior to its identification in USA and Europe. Full article

(This article belongs to the Special Issue Prions)

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Open AccessArticle Curcumin Reduces Amyloid Fibrillation of Prion Protein and Decreases Reactive Oxidative Stress

by Chi-Fen Lin, Kun-Hua Yu, Cheng-Ping Jheng, Raymond Chung and Cheng-I Lee

Pathogens 2013, 2(3), 506-519; doi:10.3390/pathogens2030506

Received: 10 July 2013 / Revised: 17 July 2013 / Accepted: 21 July 2013 / Published: 25 July 2013

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Abstract

Misfolding and aggregation into amyloids of the prion protein (PrP) is responsible for the development of fatal transmissible neurodegenerative diseases. Various studies on curcumin demonstrate promise for the prevention of Alzheimer’s disease and inhibition of PrP^res accumulation. To evaluate the effect of

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Misfolding and aggregation into amyloids of the prion protein (PrP) is responsible for the development of fatal transmissible neurodegenerative diseases. Various studies on curcumin demonstrate promise for the prevention of Alzheimer’s disease and inhibition of PrP^res accumulation. To evaluate the effect of curcumin on amyloid fibrillation of prion protein, we first investigated the effect of curcumin on mouse prion protein (mPrP) in a cell-free system. Curcumin reduced the prion fibril formation significantly. Furthermore, we monitored the change in apoptosis and reactive oxygen species (ROS) level upon curcumin treatment in mouse neuroblastoma cells (N2a). Curcumin effectively rescues the cells from apoptosis and decreases the ROS level caused by subsequent co-incubation with prion amyloid fibrils. The assays in cell-free mPrP and in N2a cells of this work verified the promising effect of curcumin on the prevention of transmissible neurodegenerative diseases. Full article

(This article belongs to the Special Issue Prions)

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Open AccessArticle Biochemical Characterization of Prion Strains in Bank Voles

by Laura Pirisinu, Stefano Marcon, Michele Angelo Di Bari, Claudia D'Agostino, Umberto Agrimi and Romolo Nonno

Pathogens 2013, 2(3), 446-456; doi:10.3390/pathogens2030446

Received: 22 May 2013 / Revised: 25 June 2013 / Accepted: 26 June 2013 / Published: 2 July 2013

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Abstract

Prions exist as different strains exhibiting distinct disease phenotypes. Currently, the identification of prion strains is still based on biological strain typing in rodents. However, it has been shown that prion strains may be associated with distinct PrP^Sc biochemical types. Taking advantage

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Prions exist as different strains exhibiting distinct disease phenotypes. Currently, the identification of prion strains is still based on biological strain typing in rodents. However, it has been shown that prion strains may be associated with distinct PrP^Sc biochemical types. Taking advantage of the availability of several prion strains adapted to a novel rodent model, the bank vole, we investigated if any prion strain was actually associated with distinctive PrP^Sc biochemical characteristics and if it was possible to univocally identify strains through PrP^Sc biochemical phenotypes. We selected six different vole-adapted strains (three human-derived and three animal-derived) and analyzed PrP^Sc from individual voles by epitope mapping of protease resistant core of PrP^Sc (PrP^res) and by conformational stability and solubility assay. Overall, we discriminated five out of six prion strains, while two different scrapie strains showed identical PrP^Sc types. Our results suggest that the biochemical strain typing approach here proposed was highly discriminative, although by itself it did not allow us to identify all prion strains analyzed. Full article

(This article belongs to the Special Issue Prions)

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Open AccessArticle Heterogeneity of the Abnormal Prion Protein (PrP^Sc) of the Chandler Scrapie Strain

by Kazuo Kasai, Yoshifumi Iwamaru, Kentaro Masujin, Morikazu Imamura, Shirou Mohri and Takashi Yokoyama

Pathogens 2013, 2(1), 92-104; doi:10.3390/pathogens2010092

Received: 9 January 2013 / Revised: 7 February 2013 / Accepted: 9 February 2013 / Published: 18 February 2013

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Abstract

The pathological prion protein, PrP^Sc, displays various sizes of aggregates. In this study, we investigated the conformation, aggregation stability and proteinase K (PK)-sensitivity of small and large PrP^Sc aggregates of mouse-adapted prion strains. We showed that small PrP^Sc aggregates,

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The pathological prion protein, PrP^Sc, displays various sizes of aggregates. In this study, we investigated the conformation, aggregation stability and proteinase K (PK)-sensitivity of small and large PrP^Sc aggregates of mouse-adapted prion strains. We showed that small PrP^Sc aggregates, previously thought to be PK-sensitive, are resistant to PK digestion. Furthermore, we showed that small PrP^Sc aggregates of the Chandler scrapie strain have greater resistance to PK digestion and aggregation-denaturation than large PrP^Sc aggregates of this strain. We conclude that this strain consists of heterogeneous PrP^Sc. Full article

(This article belongs to the Special Issue Prions)

Review

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Open AccessReview Prions and Prion-Like Pathogens in Neurodegenerative Disorders

by Caterina Peggion, Maria Catia Sorgato and Alessandro Bertoli

Pathogens 2014, 3(1), 149-163; doi:10.3390/pathogens3010149

Received: 10 January 2014 / Revised: 24 January 2014 / Accepted: 1 February 2014 / Published: 18 February 2014

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Abstract

Prions are unique elements in biology, being able to transmit biological information from one organism to another in the absence of nucleic acids. They have been identified as self-replicating proteinaceous agents responsible for the onset of rare and fatal neurodegenerative disorders—known as transmissible

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Prions are unique elements in biology, being able to transmit biological information from one organism to another in the absence of nucleic acids. They have been identified as self-replicating proteinaceous agents responsible for the onset of rare and fatal neurodegenerative disorders—known as transmissible spongiform encephalopathies, or prion diseases—which affect humans and other animal species. More recently, it has been proposed that other proteins associated with common neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease, can self-replicate like prions, thus sustaining the spread of neurotoxic entities throughout the nervous system. Here, we review findings that have contributed to expand the prion concept, and discuss if the involved toxic species can be considered bona fide prions, including the capacity to infect other organisms, or whether these pathogenic aggregates share with prions only the capability to self-replicate. Full article

(This article belongs to the Special Issue Prions)

Open AccessReview Involvement of Endogenous Retroviruses in Prion Diseases

by Yun-Jung Lee, Byung-Hoon Jeong, Eun-Kyung Choi and Yong-Sun Kim

Pathogens 2013, 2(3), 533-543; doi:10.3390/pathogens2030533

Received: 8 June 2013 / Revised: 25 July 2013 / Accepted: 9 August 2013 / Published: 12 August 2013

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Abstract

For millions of years, vertebrates have been continuously exposed to infection by retroviruses. Ancient retroviral infection of germline cells resulted in the formation and accumulation of inherited retrovirus sequences in host genomes. These inherited retroviruses are referred to as endogenous retroviruses (ERVs), and

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For millions of years, vertebrates have been continuously exposed to infection by retroviruses. Ancient retroviral infection of germline cells resulted in the formation and accumulation of inherited retrovirus sequences in host genomes. These inherited retroviruses are referred to as endogenous retroviruses (ERVs), and recent estimates have revealed that a significant portion of animal genomes is made up of ERVs. Although various host factors have suppressed ERV activation, both positive and negative functions have been reported for some ERVs in normal and abnormal physiological conditions, such as in disease states. Similar to other complex diseases, ERV activation has been observed in prion diseases, and this review will discuss the potential involvement of ERVs in prion diseases. Full article

(This article belongs to the Special Issue Prions)

Open AccessReview Kuru: A Journey Back in Time from Papua New Guinea to the Neanderthals’ Extinction

by Pawel P. Liberski

Pathogens 2013, 2(3), 472-505; doi:10.3390/pathogens2030472

Received: 19 June 2013 / Revised: 4 July 2013 / Accepted: 12 July 2013 / Published: 18 July 2013

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Abstract

Kuru, the first human transmissible spongiform encephalopathy was transmitted to chimpanzees by D. Carleton Gajdusek (1923–2008). In this review, I briefly summarize the history of this seminal discovery along its epidemiology, clinical picture, neuropathology and molecular genetics. The discovery of kuru opened new

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Kuru, the first human transmissible spongiform encephalopathy was transmitted to chimpanzees by D. Carleton Gajdusek (1923–2008). In this review, I briefly summarize the history of this seminal discovery along its epidemiology, clinical picture, neuropathology and molecular genetics. The discovery of kuru opened new windows into the realms of human medicine and was instrumental in the later transmission of Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease as well as the relevance that bovine spongiform encephalopathy had for transmission to humans. The transmission of kuru was one of the greatest contributions to biomedical sciences of the 20th century. Full article

(This article belongs to the Special Issue Prions)

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Open AccessReview Prions in Variably Protease-Sensitive Prionopathy: An Update

by Wen-Quan Zou, Pierluigi Gambetti, Xiangzhu Xiao, Jue Yuan, Jan Langeveld and Laura Pirisinu

Pathogens 2013, 2(3), 457-471; doi:10.3390/pathogens2030457

Received: 12 June 2013 / Revised: 28 June 2013 / Accepted: 2 July 2013 / Published: 5 July 2013

Cited by 3 | PDF Full-text (353 KB) | HTML Full-text | XML Full-text

Abstract

Human prion diseases, including sporadic, familial, and acquired forms such as Creutzfeldt-Jakob disease (CJD), are caused by prions in which an abnormal prion protein (PrP^Sc) derived from its normal cellular isoform (PrP^C) is the only known component. The recently-identified

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Human prion diseases, including sporadic, familial, and acquired forms such as Creutzfeldt-Jakob disease (CJD), are caused by prions in which an abnormal prion protein (PrP^Sc) derived from its normal cellular isoform (PrP^C) is the only known component. The recently-identified variably protease-sensitive prionopathy (VPSPr) is characterized not only by an atypical clinical phenotype and neuropathology but also by the deposition in the brain of a peculiar PrP^Sc. Like other forms of human prion disease, the pathogenesis of VPSPr also currently remains unclear. However, the findings of the peculiar features of prions from VPSPr and of the possible association of VPSPr with a known genetic prion disease linked with a valine to isoleucine mutation at residue 180 of PrP reported recently, may be of great importance in enhancing our understanding of not only this atypical human prion disease in particular, but also other prion diseases in general. In this review, we highlight the physicochemical and biological properties of prions from VPSPr and discuss the pathogenesis of VPSPr including the origin and formation of the peculiar prions. Full article

(This article belongs to the Special Issue Prions)

Open AccessReview The Functional Role of Prion Protein (PrP^C) on Autophagy

by Hae-Young Shin, Jae-Min Oh and Yong-Sun Kim

Pathogens 2013, 2(3), 436-445; doi:10.3390/pathogens2030436

Received: 2 May 2013 / Revised: 11 June 2013 / Accepted: 18 June 2013 / Published: 26 June 2013

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Abstract

Cellular prion protein (PrP^C) plays an important role in the cellular defense against oxidative stress. However, the exact protective mechanism of PrP^C is unclear. Autophagy is essential for survival, differentiation, development, and homeostasis in several organisms. Although the role that

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Cellular prion protein (PrP^C) plays an important role in the cellular defense against oxidative stress. However, the exact protective mechanism of PrP^C is unclear. Autophagy is essential for survival, differentiation, development, and homeostasis in several organisms. Although the role that autophagy plays in neurodegenerative disease has yet to be established, it is clear that autophagy-induced cell death is observed in neurodegenerative disorders that exhibit protein aggregations. Moreover, autophagy can promote cell survival and cell death under various conditions. In this review, we describe the involvement of autophagy in prion disease and the effects of PrP^C. Full article

(This article belongs to the Special Issue Prions)

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Research

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Review

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Guest Editor Dr. Wen-Quan Zou Associate Professor of Departments of Pathology and Neurology, Associate Director of National Prion Disease Pathology Surveillance Center, Case Western Reserve University School of Medicine, Adelbert Road, Room 403, Cleveland, OH 44106, USA Website \| E-Mail Phone: 216-368-8993 Fax: +1 216 368 2546 Interests: prions; prion diseases; neurodegenerative disorders; protein misfolding disorders; protein aggregations; neuroscience; alzheimer’s disease; and glycosylation
Guest Editor Prof. Dr. Xiao-Ping Dong Director of Prion Research Group, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changbai Rd 155, Beijing 102206, People's Republic of China E-Mail Fax: +86 10 58900815 Interests: prions; prion diseases
Guest Editor Prof. Dr. Yong-Sun Kim Professor of Department of Microbiology and Immunology, College of Medicine, Director of Ilsong Institute of Life Science, Executive Vice President for Health & Biomedical Sciences, Hallym University, 1605-4, Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060, Korea Website \| E-Mail Phone: +82 31 381 0972 Fax: +82 31 388 3427 Interests: prion diseases; endogenous retrovirus; oxidative stress; protein citrullination; autophagy and neurodegenerative disorders