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Won-Hee Nam, Young Pyo Choi
Normal monomeric tau can be converted into pathogenic aggregates and acquire protease resistance in a prion-like manner. This acquisition of partial protease-resistance in tau aggregates has to date only been partially investigated in various studies exploring the prion-like properties of tau. In this study, we induced the aggregation of tau repeat domain (RD) in cultured cells using detergent insoluble fractions of Alzheimer's brain tissue as seeds. The seeded aggregation of tau RD in cultured cells formed a ~7 kDa protease-resistant fragment in contrast to the ~12 kDa tau fragment characteristic of the AD seeds, suggesting that the in vitro generated tau aggregates were conformationally distinct from parent seeds...
November 13, 2018: Prion
Yasushi Iwasaki, Rina Hashimoto, Yufuko Saito, Ikuko Aiba, Akira Inukai, Akio Akagi, Maya Mimuro, Hiroaki Miyahara, Tetsuyuki Kitamoto, Mari Yoshida
An 83-year-old Japanese man presented with gait disturbance followed by rapidly-progressive cognitive impairment. Magnetic resonance diffusion-weighted images showed extensive hyperintense regions in the cerebral cortex. Four weeks after symptom onset, myoclonus appeared, and the patient developed difficulty swallowing; intravenous peripheral continuous infusions without vitamin supplementation were administered during the last two months of the patient's life. The patient reached the akinetic mutism state and died 12 weeks after symptom onset due to sepsis...
November 8, 2018: Prion
Fumiko Furukawa, Nobuo Sanjo, Atsushi Kobayashi, Tsuyoshi Hamaguchi, Masahito Yamada, Tetsuyuki Kitamoto, Hidehiro Mizusawa, Takanori Yokota
Although colocalization of amyloid β (Aβ) with prion protein (PrP) in the kuru plaque has previously been observed in the brain of prion diseases patients, the participating Aβ species has not been identified. Here, we present an immunohistochemical assessment of the brain and spinal cord of a 69-year-old Japanese female patient with Gerstmann-Sträussler-Scheinker disease with a P105L mutation on the PRNP gene (GSS-P105L). Immunohistochemical assessment of serial brain sections was performed using anti-PrP and -Aβ antibodies in the hippocampus, frontal and occipital lobes...
November 5, 2018: Prion
Soyoun Hwang, Eric M Nicholson
Propagation of transmissible spongiform encephalopathies involves the conversion of cellular prion protein, PrPC , into a misfolded oligomeric form, PrPSc . The most common hereditary prion disease is a genetic form of Creutzfeldt-Jakob disease in humans, in which a mutation in the prion gene results in a glutamic acid to lysine substitution at position 200 (E200K) in PrP. In cattle, the analogous amino acid substitution is found at residue 211 (E211K) and has been associated with a case of bovine spongiform encephalopathy...
October 24, 2018: Prion
Junliang Yuan, Shuangkun Wang, Wenli Hu
Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal progressive neurodegenerative disease. Multimodal approaches, including electroencephalogram, diffusion-weighted imaging (DWI) of brain MRI, and cerebrospinal fluid biomarkers, have been applied to increase the diagnostic accuracy of sCJD. Although previous studies suggested DWI could be the most useful modality for sCJD diagnosis, whether metabolism changes underlying in sCJD are still poorly understood. To the best of our knowledge, there are only one case using the technique of arterial spin labeling (ASL) to detection and follow-up of perfusion changes in CJD...
September 18, 2018: Prion
Carol L Ladner-Keay, Li Ross, Rolando Perez-Pineiro, Lun Zhang, Trent C Bjorndahl, Neil Cashman, David S Wishart
Prion diseases are caused by the conversion of normal cellular prion proteins (PrP) into lethal prion aggregates. These prion aggregates are composed of proteinase K (PK) resistant fibrils and comparatively PK-sensitive oligomers. Currently there are no anti-prion pharmaceuticals available to treat or prevent prion disease. Methods of discovering anti-prion molecules rely primarily on relatively complex cell-based, tissue slice or animal-model assays that measure the effects of small molecules on the formation of PK-resistant prion fibrils...
September 18, 2018: Prion
Lary C Walker, David G Lynn, Yury O Chernoff
The recent Research Framework proposed by the US National Institute on Aging and the Alzheimer's Association (NIA-AA) recommends that Alzheimer's disease be defined by its specific biology rather than by non-specific neurodegenerative and syndromal features. By affirming markers of abnormal Aβ and tau proteins as the essential pathobiological signature of Alzheimer's disease, the Framework tacitly reinforces the amyloid (Aβ) cascade as the leading theory of Alzheimer pathogenesis. In light of recent evidence that the cascade is driven by the misfolding and templated aggregation of Aβ and tau, we believe that an empirically grounded Standard Model of Alzheimer's pathogenesis is within reach...
September 17, 2018: Prion
Atsushi Okamoto, Nao Hosoda, Shin-Ichi Hoshino
The yeast Saccharomyces cerevisiae has proven to be a useful model system to investigate the mechanism of prion generation and inheritance, to which studies in Sup35 made a great contribution. Recent studies demonstrated that 'protein misfolding and aggregation' (i.e. amyloidogenesis) is a common principle underlying the pathogenesis of neurodegenerative diseases including prion, amyotrophic lateral sclerosis (ALS), Perkinson's (PD), Alzheimer's (AD) diseases and polyglutamine (polyQ) diseases such as spinocerebellar ataxia (SCA) and Hantington's disease (HD)...
September 9, 2018: Prion
Marta Díaz-Caballero, Maria Rosario Fernández, Susanna Navarro, Salvador Ventura
Protein misfolding and aggregation into highly ordered fibrillar structures have been traditionally associated with pathological processes. Nevertheless, nature has taken advantage of the particular properties of amyloids for functional purposes, like in the protection of organisms against environmental changing conditions. Over the last decades, these fibrillar structures have inspired the design of new nanomaterials with intriguing applications in biomedicine and nanotechnology such as tissue engineering, drug delivery, adhesive materials, biodegradable nanocomposites, nanowires or biosensors...
September 8, 2018: Prion
Emmanuel E Comoy, Jacqueline Mikol, Jean-Philippe Deslys
The recently reevaluated high prevalence of healthy carriers (1/2,000 in UK) of variant Creutzfeldt-Jakob Disease (v-CJD), whose blood might be infectious, suggests that the evolution of this prion disease might not be under full control as expected. After experimental transfusion of macaques and conventional mice with blood derived from v-CJD exposed (human and animal) individuals, we confirmed in these both models the transmissibility of v-CJD, but we also observed unexpected neurological syndromes transmissible by transfusion: despite their prion etiology confirmed through transmission experiments, these original cases would escape classical prion diagnosis, notably in the absence of detectable abnormal PrP with current techniques...
August 16, 2018: Prion
Gregory A Newby, Can Kayatekin
Microbial prions facilitate a variety of phenotypic switches. Recently-developed tools that can directly interrogate, in the living cell, the aggregation state of a protein have enabled a wider range of experiments for prion-mediated behaviors. With such tools, the roles of the yeast prion [SWI+ ] in migration and mating were studied. Although [SWI+ ] cells were consistently less fit than their [swi- ] counterparts under traditional laboratory conditions, in these new phenotypic paradigms [SWI+ ] cells demonstrated a distinct advantage...
July 24, 2018: Prion
Yong-Chan Kim, Min-Ju Jeong, Byung-Hoon Jeong
Abnormal structural changes of the prion protein (PrP) are the cause of prion disease in a wide range of mammals. However, spontaneous infected cases have not been reported in chicken. Genetic variations of the prion protein gene (PRNP) may impact susceptibility to prion disease but have not been investigated thus far. Because an investigation of the chicken PRNP can improve the understanding of characteristics related to resistance to prion disease, research on the chicken PRNP is highly desirable. In this study, we investigated the genetic characteristics of the chicken PRNP gene...
July 14, 2018: Prion
Qi Shi, Jian-Le Li, Yue Ma, Li-Ping Gao, Kang Xiao, Jing Wang, Wei Zhou, Cao Chen, Yan-Jun Guo, Xiao-Ping Dong
The levels of ryanodine receptors (RyRs) are usually increased in the brains of human Alzheimer disease (AD) and AD animal models. To evaluate the underlying alteration of brain RyRs in prion disease, scrapie infected cell line SMB-S15 and its infected mice were tested. RyR2 specific Western blots revealed markedly decreased RyR2 levels both in the cells and in the brains of infected mice. Assays of the brain samples of other scrapie (agents 139A and ME7) infected mice collected at different time-points during incubation period showed time-dependent decreases of RyR2...
June 7, 2018: Prion
Jie Li, Shaoli Zhang, Sarantsetseg Erdenee, Xiuzhu Sun, Ruihua Dang, Yongzhen Huang, Chuzhao Lei, Hong Chen, Hongwei Xu, Yong Cai, Xianyong Lan
Studies of the ovine prion-related protein (testis-specific) gene (PRNT), including studies of genetic diversity, have highlighted its potential relationship to scrapie infection and economically important ovine traits. PRNT was previously reported to be highly polymorphic in Portuguese sheep. To characterize genetic polymorphisms in this gene in Asian sheep, a direct sequencing method was used to detect polymorphic loci in PRNT in 285 individual sheep from four Chinese and one Mongolian breeds. Seven SNP variants in PRNT were identified, including three novel variants (g...
June 5, 2018: Prion
Giuseppe Legname, Tommaso Virgilio, Edoardo Bistaffa, Chiara Maria Giulia De Luca, Marcella Catania, Paola Zago, Elisa Isopi, Ilaria Campagnani, Fabrizio Tagliavini, Giorgio Giaccone, Fabio Moda
Pin1 is a peptidyl-prolyl isomerase that induces the cis-trans conversion of specific Ser/Thr-Pro peptide bonds in phosphorylated proteins, leading to conformational changes through which Pin1 regulates protein stability and activity. Since down-regulation of Pin1 has been described in several neurodegenerative disorders, including Alzheimer's Disease (AD), Parkinson's Disease (PD) and Huntington's Disease (HD), we investigated its potential role in prion diseases. Animals generated on wild-type (Pin1+/+ ), hemizygous (Pin1+/- ) or knock-out (Pin1-/- ) background for Pin1 were experimentally infected with RML prions...
March 4, 2018: Prion
Stefano Martellucci, Valeria Manganelli, Costantino Santacroce, Francesca Santilli, Luca Piccoli, Maurizio Sorice, Vincenzo Mattei
Cellular prion protein (PrPC ) is expressed in a wide variety of stem cells in which regulates their self-renewal as well as differentiation potential. In this study we investigated the presence of PrPC in human dental pulp-derived stem cells (hDPSCs) and its role in neuronal differentiation process. We show that hDPSCs expresses early PrPC at low concentration and its expression increases after two weeks of treatment with EGF/bFGF. Then, we analyzed the association of PrPC with gangliosides and EGF receptor (EGF-R) during neuronal differentiation process...
March 4, 2018: Prion
Sol Moe Lee, Wonseok Lee, Yeong Seon Lee, Jin-Soo Yoo, Soo-Jung Park, Heebal Kim, Su Yeon Kim
Prion diseases are fatal neurodegenerative disorders that affect humans and animals. Although various small molecules have been evaluated for application in the treatment of prion diseases, none have been shown to be efficacious. Expanding our knowledge of these molecules is important for understanding of the complex mechanisms of prion diseases. To improve access to the scattered information on small molecules related to prion diseases, we built a database of therapeutic molecules associated with prion diseases (THERPA, therpa...
March 4, 2018: Prion
Soochan Kim, Sinsuk Han, Taehyun Kim, Jeehoon Nam, Yong-Sun Kim, Eun-Kyoung Choi, Mi-Yeon Kim
We previously reported that mice intracerebrally inoculated with the mouse-adapted scrapie strain ME7 have markedly diminished T zones in the spleen due to the decreased expression of CCL19 and CCL21. In addition, follicular dendritic cell networks in germinal centers were larger in ME7-infected spleens compared to uninfected spleens. As an extension of that study, we set out to determine how ME7 infection affects spleen structure and follicular helper T (Tfh) cell responses in mice. For this study, mice were intraperitoneally inoculated with brain homogenate of the ME7 inoculum and spleens were analyzed 50, 130, and 200 days after inoculation and compared with those from uninfected mice...
March 4, 2018: Prion
Jing Wang, Kang Xiao, Wei Zhou, Chen Gao, Cao Chen, Qi Shi, Xiao-Ping Dong
Gerstmann-Sträussler-Scheinker disease (GSS) with the P102L mutation in PRNP gene is characterized with progressive cerebellar dysfunction clinically and PrPSc plaques neurologically. Due to the cerebellar ataxia in the early stage, GSS P102L is often misdiagnosed as other neurodegenerative disorders. We presented here a 49-year-old female patient with proven P102L PRNP mutation, and three heterologous mutations in hereditary ataxias associated gene SYNE1, including p.V3643L, p.M3376V and p.T2860A. The patient appeared progressive unsteady gait in early stage and developed the Creutzfeldt-Jacob disease (CJD) - associated clinical manifestations, including progressive dementia, myoclonus, pyramidal and extrapyramidal signs...
March 4, 2018: Prion
Nicholas J Haley, Jürgen A Richt, Kristen A Davenport, Davin M Henderson, Edward A Hoover, Matteo Manca, Byron Caughey, Douglas Marthaler, Jason Bartz, Sabine Gilch
Amplification assays for transmissible spongiform encephalopathies have been in development for close to 15 years, with critical implications for the postmortem and antemortem diagnosis of human and animal prion diseases. Little has been published regarding the structured development, implementation and interpretation of experiments making use of protein misfolding cyclic amplification (PMCA) and real time quaking-induced conversion (RT-QuIC), and our goal with this Perspectives manuscript is to offer a framework which might allow for more efficient expansion of pilot studies into diagnostic trials in both human and animal subjects...
March 4, 2018: Prion
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