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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 6, 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...
February 22, 2018: Prion
Nicholas J Haley, Davin M Henderson, Sarah Wycoff, Joanne Tennant, Edward A Hoover, Dan Love, Ed Kline, Aaron Lehmkuhl, Bruce Thomsen
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) affecting members of the cervid species, and is one of the few TSEs with an expanding geographic range. Diagnostic limitations, efficient transmission, and the movement of infected animals are important contributing factors in the ongoing spread of disease. Managing CWD in affected populations has proven difficult, relying on population reduction in the case of wild deer and elk, or quarantine and depopulation in farmed cervids...
February 9, 2018: Prion
Natsumi Saito, Tomohiko Ishihara, Kensaku Kasuga, Mana Nishida, Takanobu Ishiguro, Hiroaki Nozaki, Takayoshi Shimohata, Osamu Onodera, Masatoyo Nishizawa
We report a Japanese patient with spinocerebellar ataxia type 31 (SCA31) and sporadic Creutzfeldt-Jakob disease (sCJD). A 52-year-old man developed progressive cognitive impairment after the appearance of cerebellar symptoms. Brain MR diffusion-weighted imaging (DWI) demonstrated a slowly expanding hyperintense lesion in the cerebral cortex. The patient was finally diagnosed as having both SCA31 and sCJD by identification of genetic mutations and by real-time quaking-induced conversion (RT-QUIC) analysis of the cerebrospinal fluid (CSF), respectively...
February 7, 2018: Prion
Jie Li, Sarantsetseg Erdenee, Shaoli Zhang, Zhenyu Wei, Meng Zhang, Yunyun Jin, Hui Wu, Hong Chen, Xiuzhu Sun, Hongwei Xu, Yong Cai, Xianyong Lan
Prion protein (PRNP) gene is well known for affecting mammal transmissible spongiform encephalopathies (TSE), and is also reported to regulate phenotypic traits (e.g. growth traits) in healthy ruminants. To identify the insertion/deletion (indel) variations of the PRNP gene and evaluate their effects on growth traits, 768 healthy individuals from five sheep breeds located in China and Mongolia were identified and analyzed. Herein, four novel indel polymorphisms, namely, Intron-1-insertion-7bp (I1-7bp), Intron-2-insertion-15bp (I2-15bp), Intron-2-insertion-19bp (I2-19bp), and 3' UTR-insertion-7bp (3' UTR-7bp), were found in the sheep PRNP gene...
February 2, 2018: Prion
Lois E Greene, Xiaohong Zhao, Evan Eisenberg
The yeast [PSI+ ] prion, which is the amyloid form of Sup35, has the unusual property of being cured not only by the inactivation of, but also by the overexpression of Hsp104. Even though this latter observation was made more than two decades ago, the mechanism of curing by Hsp104 overexpression has remained controversial. This question has been investigated in depth by our laboratory by combining live cell imaging of GFP-labeled Sup35 with standard plating assays of yeast overexpressing Hsp104. We will discuss why the curing of [PSI+ ] by Hsp104 overexpression is not compatible with a mechanism of either inhibition of severing of the prion seeds or asymmetric segregation of the seeds...
February 2, 2018: Prion
Sebastian Jung, Jörg Tatzelt
Impaired transport of intrinsically disordered proteins through the Sec61 and SecY translocon; implications for prion diseases.
February 1, 2018: Prion
Natalia Fernández-Borges, Hasier Eraña, Joaquín Castilla
Historically, the observation of naturally occurring cases of prion disease led to the classification of different susceptibility grades and to the designation of prion resistant species. However, the development of highly efficient in vitro prion propagation systems and the generation of ad hoc transgenic models allowed determining that leporidae and equidae families have been erroneously considered resistant to prion infection. On the contrary, similar approaches revealed an unexpected high level of resistance of the canidae family...
February 1, 2018: Prion
Joanna Bielewicz, Anna Szczepańska-Szerej, Magdalena Ogórek, Piotr Dropko, Katarzyna Wojtal, Konrad Rejdak
We reported the case of a patient with Wernicke-Korsakoff syndrome (WKs) as an early clinical manifestation of sporadic Creutzfeld-Jakob disease (sCJD). The 66-year-old female complained of dizziness and imbalance which mostly occurred while walking. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk as well as memory disturbances with confabulations. The disturbances increased during the course of the disease, which led to the death of the patient four months after the appearance of the signs...
January 30, 2018: Prion
Daniel Samorodnitsky, Eric M Nicholson
Misfolding of the normally folded prion protein of mammals (PrPC) into infectious fibrils causes a variety of diseases, from scrapie in sheep to chronic wasting disease (CWD) in cervids. The misfolded form of PrPC, termed PrPSc, or in this case PrPCWD, interacts with PrPC to create more PrPCWD. This process is not clearly defined but is affected by the presence and interactions of biotic and abiotic cofactors. These include nucleic acids, lipids, glycosylation, pH, and ionic character. PrPC has been shown to act as a copper-binding protein in vivo, though it also binds to other divalents as well...
January 9, 2018: Prion
Elena De Cecco, Giuseppe Legname
Synucleinopathies are a group of neurodegenerative diseases characterized by the accumulation of α-synuclein amyloids in several regions of the brain. α-Synuclein fibrils are able to spread via cell-to-cell transfer, and once inside the cells, they can template the misfolding and aggregation of the endogenous α-synuclein. Multiple mechanisms have been shown to participate in the process of propagation: endocytosis, tunneling nanotubes and micropinocytosis. Recently, we published a research showing that the cellular form of the prion protein (PrPC) acts as a receptor for α-synuclein amyloid fibrils, facilitating their internalization through and endocytic pathway...
January 8, 2018: Prion
Sei-Kyoung Park, Fatih Arslan, Vydehi Kanneganti, Sami J Barmada, Pravinkumar Purushothaman, Subhash Chandra Verma, Susan W Liebman
TDP-43 and FUS are DNA/RNA binding proteins associated with neuronal inclusions in amyotrophic lateral sclerosis (ALS) patients. Other neurodegenerative diseases are also characterized by neuronal protein aggregates, e.g. Huntington's disease, associated with polyglutamine (polyQ) expansions in the protein huntingtin. Here we discuss our recent paper establishing similarities between aggregates of TDP-43 that have short glutamine and asparagine (Q/N)-rich modules and are soluble in detergents, with those of polyQ and PIN4C that have large Q/N-rich domains and are detergent-insoluble...
January 8, 2018: Prion
Alessandro Bertoli, M Catia Sorgato
Calcium (Ca2+ ) is an intracellular second messenger that ubiquitously masters remarkably diverse biological processes, including cell death. Growing evidence substantiates an involvement of the prion protein (PrPC ) in regulating neuronal Ca2+ homeostasis, which could rationalize most of the wide range of functions ascribed to the protein. We have recently demonstrated that PrPC controls extracellular Ca2+ fluxes, and mitochondrial Ca2+ uptake, in neurons stimulated with glutamate (De Mario et al., J Cell Sci 2017; 130:2736-46), suggesting that PrPC protects neurons from threatening Ca2+ overloads and excitotoxicity...
January 5, 2018: Prion
Chen Gao, Qiang Shi, Jing Wei, Wei Zhou, Kang Xiao, Jing Wang, Qi Shi, Xiao-Ping Dong
Prion diseases are a group of fatal neurodegenerative disorders that affect humans and animals. Besides of the pathological agent, prion, there are some elements that can influence or determine susceptibility to prion infection and the clinical phenotype of the diseases, e.g., the polymorphism in PRNP gene. Another polymorphism in ZBTB38-RASA2 has been observed to be associated with the susceptibility of sporadic Creutzfeldt-Jacob disease (sCJD) in UK. MicroRNAs are endogenous small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation...
January 2, 2018: Prion
Akio Akagi, Yasushi Iwasaki, Maya Mimuro, Tetsuyuki Kitamoto, Masahito Yamada, Mari Yoshida
In comparison to sporadic Creutzfeldt-Jakob disease (sCJD) with MM1-type and MM2- cortical (MM2C)-type, genetic CJD with a prion protein gene V180I mutation (V180I gCJD) is clinically characterized by onset at an older age, slower progress, and the absence of visual disturbances or cerebellar symptoms. In terms of pathological characteristics, gliosis and neuronal loss are generally milder in degree, and characteristic spongiform change can be observed at both the early and advanced stages. However, little is known on the progress of spongiform change over time or its mechanisms...
December 21, 2017: Prion
Michael Solarski, Hansen Wang, Holger Wille, Gerold Schmitt-Ulms
The amyloid beta (Aβ) peptide is central to the pathogenesis of Alzheimer's disease (AD). Insights into Aβ-interacting proteins are critical for understanding the molecular mechanisms underlying Aβ-mediated toxicity. We recently undertook an in-depth in vitro interrogation of the Aβ1-42 interactome using human frontal lobes as the biological source material and taking advantage of advances in mass spectrometry performance characteristics. These analyses uncovered the small cyclic neuropeptide somatostatin (SST) to be the most selectively enriched binder to oligomeric Aβ1-42...
December 1, 2017: Prion
(no author information available yet)
No abstract text is available yet for this article.
November 16, 2017: Prion
Beata Sikorska, Agata Gajos, Andrzej Bogucki, Emil Zielonka Christina Sigurdson, Pawel P Liberski
We report here on the ultrastructure of amyloid plaques in chronic wasting disease (CWD) transmitted to Tg20 transgenic mice overexpressing prion protein (PrP(c)). We identified three main types of amyloid deposits in mCWD: large amyloid deposits, unicentric plaques similar to kuru plaques in human prion diseases and multicentric plaques reminiscent of plaques typical of GSS. The most unique type of plaques were large subpial amyloid deposits. They were composed of large areas of amyloid fibrils but did not form "star-like" appearances of unicentric plaques...
November 6, 2017: Prion
Dimitri Renard, Giovanni Castelnovo, Laurent Collombier, Eric Thouvenot, Vincent Boudousq
OBJECTIVE: To assess the relationship between clinical pattern and cerebral glucose metabolism on [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in Creutzfeldt-Jakob disease (CJD). METHODS: Predefined clinical signs (ataxia, visual, pyramidal, myoclonus, limb apraxia, limb dystonia, sensory, parkinsonism, and corticobasal syndrome [CBS]) and FDG-PET data were assessed in consecutive CJD patients. Two types of statistical parametric mapping (SPM) analyses, using stringent level of significance p<0...
November 3, 2017: Prion
Suehiro Sakaguchi, Keiji Uchiyama
Conformational conversion of the cellular prion protein, PrP(C), into the abnormally folded isoform of prion protein, PrP(Sc), which leads to marked accumulation of PrP(Sc) in brains, is a key pathogenic event in prion diseases, a group of fatal neurodegenerative disorders caused by prions. However, the exact mechanism of PrP(Sc) accumulation in prion-infected neurons remains unknown. We recently reported a novel cellular mechanism to support PrP(Sc) accumulation in prion-infected neurons, in which PrP(Sc) itself promotes its accumulation by evading the cellular inhibitory mechanism, which is newly identified in our recent study...
November 3, 2017: Prion
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