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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
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
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...
December 11, 2017: 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...
December 11, 2017: 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...
December 8, 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
Sireesha Manne, Naveen Kondru, Tracy Nichols, Aaron Lehmkuhl, Bruce Thomsen, Rodger Main, Patrick Halbur, Somak Dutta, Anumantha G Kanthasamy
Prion diseases are transmissible spongiform encephalopathies (TSEs) characterized by fatal, progressive neurologic diseases with prolonged incubation periods and an accumulation of infectious misfolded prion proteins. Antemortem diagnosis is often difficult due to a long asymptomatic incubation period, differences in the pathogenesis of different prions, and the presence of very low levels of infectious prion in easily accessible samples. Chronic wasting disease (CWD) is a TSE affecting both wild and captive populations of cervids, including mule deer, white-tailed deer, elk, moose, muntjac, and most recently, wild reindeer...
November 3, 2017: Prion
Tae-Young Suh, In Soon Roh, Hyo-Jin Kim, Peter C Griffiths, Kyung Je Park, Hoo Chang Park, James Hope, Hae Eun Kang, Dae-Yong Kim, Hyun Joo Sohn
M2B cells with persistent classical bovine spongiform encephalopathy (C-BSE) have been established previously. In this study, we performed strain characterization of the M2B cell line in bovine PrP(C) overexpressing mice (Tg 1896). Mice intracranially inoculated with M2B cells and C-BSE survived for 451 ± 7 and 465 ± 31 d post inoculation, respectively. Although biochemical properties, including deglycosylation and conformational stability, differed between M2B cells and C-BSE, inoculation with M2B cell lysate and C-BSE resulted in comparable phenotypes...
November 3, 2017: Prion
Ricardo Krause Martinez de Souza, Nalini Drieli Josviak, Meire Silva Batistela, Paulo Sergio Faro Santos, Michele Christine Landemberger, Ricardo Ramina
Here, we report the first case of V180I rare mutation in a Brazilian woman whose clinical condition started with memory impairment for recent events and insomnia with 2 months of evolution, without any other alterations in neurological examination. Both the electroencephalogram (EEG) and the routine biochemical examination of cerebrospinal fluid (CSF) were normal. CSF 14-3-3 protein search was positive. Magnetic resonance imaging (MRI) of the encephalon showed findings suggestive of Creutzfeldt-Jakob disease, confirmed by sequencing of PRNP gene that reveal V180I mutation also homozygosity for methionine at codon 129 (M129M)...
November 2, 2017: Prion
Yuichi Hayashi
No abstract text is available yet for this article.
November 2, 2017: Prion
James Alibhai, Abigail Diack, Jean Manson
Chronic neurodegenerative diseases, such as prion diseases or Alzheimer's disease, are associated with progressive accumulation of host proteins which misfold and aggregate. Neurodegeneration is restricted to specific neuronal populations which show clear accumulation of misfolded proteins, whilst neighbouring neurons remain unaffected. Such data raise interesting questions about the vulnerability of specific neuronal populations to neurodegeneration and much research has concentrated only on the mechanisms of neurodegeneration in afflicted neuronal populations...
October 12, 2017: Prion
Yuichi Hayashi, Megumi Yamada, Akio Kimura, Takahiko Asano, Katsuya Satoh, Tetsuyuki Kitamoto, Maokoto Yoneda, Takashi Inuzuka
We report the case of a 76-year-old woman presenting with 47-month history of progressive dementia and cortical blindness with no family history. Antibodies against thyroid glands and the N-terminus of α-enolase (NAE) were detected in her serum. Neurological examination revealed progressive dementia, frontal signs, visual disturbance, and exaggerated bilateral tendon reflexes in both legs. Diffusion MRI showed cortical hyper-intensities in the bilateral occipital and parietal, and the left frontal and temporal cortices...
October 2, 2017: Prion
Alex J McDonald, Bei Wu, David A Harris
The normal function of PrP(C), the cellular prion protein, has remained mysterious since its first description over 30 years ago. Amazingly, although complete deletion of the gene encoding PrP(C) has little phenotypic consequence, expression in transgenic mice of PrP molecules carrying certain internal deletions produces dramatic neurodegenerative phenotypes. In our recent paper, (1) we have demonstrated that the flexible, N-terminal domain of PrP(C) possesses toxic effector functions, which are regulated by a docking interaction with the structured, C-terminal domain...
September 29, 2017: Prion
Pardis Tabaee Damavandi, Martin T Dove, Richard W Pickersgill
BACKGROUND: Sporadic fatal insomnia (sFI) is a rapid progressive neurodegenerative disease characterised by gradual to perpetual insomnia, followed by dysautonomia, coma and death. (1) The cause of sFI was recently mapped to a mutation in a protein, the prion, found in the human brain. It is the unfolding of the prion that leads to the generation of toxic oligomers that destroy brain tissue and function. Recent studies have confirmed that a methionine mutation at codon 129 of the human Prion is characteristic of sFI...
September 3, 2017: Prion
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