The Experts below are selected from a list of 915 Experts worldwide ranked by ideXlab platform
Pietro Cortelli - One of the best experts on this subject based on the ideXlab platform.
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LETTERS Alteration of the Serotoninergic System in Fatal Familial Insomnia
2013Co-Authors: Pietro Cortelli, Pasquale Montagna, Ronald Polinsky, Elio LugaresiAbstract:We read with interest that Wanschitz and colleagues 1 found a substantial increase in tryptophan hydroxylase-immunoreactive neurons in the pons (superior central nucleus) and medulla (raphe obscurus nucleus) of Fatal Familial Insomnia (FFI) patients, suggesting that a serotoninergic system impairment represents the functional substrate of some typical FFI symptoms. We report the lumbar cerebrospinal fluid (CSF) concentrations of monoamine metabolites in 3 FFI subjects (1 female) of 2 unrelated Italian families already described. 2 We measured 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) by a gas chromatographic, mass spectroscopic method previously described. 3,4 The central component of MHPG was calculated according to the formula [total CSF MHPG] � 0.9 [free plasma MHPG]. 4 FFI patients had the typical poin
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Oneiric stupor: the peculiar behaviour of agrypnia excitata.
Sleep Medicine, 2011Co-Authors: Pietro Guaraldi, Pasquale Montagna, Elio Lugaresi, Pietro Cortelli, Paolo Tinuper, Giovanna Calandra-buonaura, Rossana Terlizzi, Federica ProviniAbstract:Agrypnia excitata (AE) is a syndrome characterized by the inability to sleep associated with a generalized motor and autonomic over-activation. AE is caused by a thalamo-limbic system dysfunction and comprises three different conditions: Fatal Familial Insomnia (FFI), Delirium Tremens (DT), and Morvan Syndrome (MS). Oneiric Stupor episodes (OS) are the peculiar motor behaviour of AE. During OS patients perform simple automatic gestures mimicking daily-life activities. This paper is the first description of the different characteristics of OS in two patients with MS and another with FFI, emphasizing the specific clinical features that reliably differentiate OS from REM sleep behaviour disorders.
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morvan s syndrome peripheral and central nervous system and cardiac involvement with antibodies to voltage gated potassium channels
Brain, 2001Co-Authors: Rocco Liguori, Giuseppe Plazzi, Patrizia Avoni, Pietro Cortelli, Angela Vincent, Linda Clover, A Baruzzi, T Carey, P Gambetti, E LugaresiAbstract:Summary Morvan’s ‘fibrillary chorea’ or Morvan’s syndrome is characterized by neuromyotonia (NMT), pain, hyperhydrosis, weight loss, severe Insomnia and hallucinations. We describe a man aged 76 years with NMT, dysautonomia, cardiac arrhythmia, lack of slow-wave sleep and abnormal rapid eye movement sleep. He had raised serum antibodies to voltage-gated K channels (VGKC), oligoclonal bands in his CSF, markedly increased serum norepinephrine, increased serum cortisol and reduced levels and absent circadian rhythms of prolactin and melatonin. The neurohormonal findings and many of the clinical features were very similar to those in Fatal Familial Insomnia, a hereditary prion disease that is associated with thalamic degenerative changes. Strikingly, however, all symptoms in our MFC patient improved
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evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity
Science, 1996Co-Authors: Glenn C Telling, Pasquale Montagna, James A Mastrianni, Stephen J Dearmond, Pietro Cortelli, Piero Parchi, E Lugaresi, Pierluigi Gambetti, Ruth Gabizon, Stanley B PrusinerAbstract:The fundamental event in prion diseases seems to be a conformational change in cellular prion protein (PrP C ) whereby it is converted into the pathologic isoform PrP Sc . In Fatal Familial Insomnia (FFI), the protease-resistant fragment of PrP Sc after deglycosylation has a size of 19 kilodaltons, whereas that from other inherited and sporadic prion diseases is 21 kilodaltons. Extracts from the brains of FFI patients transmitted disease to transgenic mice expressing a chimeric human-mouse PrP gene about 200 days after inoculation and induced formation of the 19-kilodalton PrP Sc fragment, whereas extracts from the brains of Familial and sporadic Creutzfeldt-Jakob disease patients produced the 21-kilodalton PrP Sc fragment in these mice. The results presented indicate that the conformation of PrP Sc functions as a template in directing the formation of nascent PrP Sc and suggest a mechanism to explain strains of prions where diversity is encrypted in the conformation of PrP Sc .
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Fatal Familial Insomnia and Familial creutzfeldt jakob disease different prion proteins determined by a dna polymorphism
Proceedings of the National Academy of Sciences of the United States of America, 1994Co-Authors: L Monari, Pasquale Montagna, Robert B Petersen, Pietro Cortelli, Piero Parchi, Shu G Chen, P Brown, Jacqueline Mikol, F Gray, Bernardino GhettiAbstract:Abstract Fatal Familial Insomnia and a subtype of Creutzfeldt-Jakob disease, two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asp-178-->Asn) but segregate with different genotypes determined by this mutation and the methionine-valine polymorphism at codon 129 of the prion protein gene. The abnormal isoforms of the prion protein in these two diseases were found to differ both in the relative abundance of glycosylated forms and in the size of the protease-resistant fragments. The size difference was consistent with a different protease cleavage site, suggesting a different conformation of the protease-resistant prion protein present in the two diseases. These differences are likely to be responsible for the type and location of the lesions that characterize these two diseases. Therefore, the combination of the mutation at codon 178 and the polymorphism at codon 129 determines the disease phenotype by producing two altered conformations of the prion protein.
Piero Parchi - One of the best experts on this subject based on the ideXlab platform.
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Mortality and classification of all definite and probable TSE patients.
2013Co-Authors: Casper Jansen, Piero Parchi, Sabina Capellari, Rosaria Strammiello, Carla A. Ibrahim-verbaas, Maaike Schuur, Patrizia Corrado, Matthew T. Bishop, Willem A. Van Gool, Marcel M. VerbeekAbstract:TSE = Transmissible Spongiform Encephalopathy; CJD = Creutzfeldt-Jakob disease; sCJD = sporadic Creutzfeldt-Jakob disease; GSS = Gerstmann-Sträussler-Scheinker disease; PrP-CAA = prion protein cerebral amyloid angiopathy; FFI = Fatal Familial Insomnia; VPSPr = variably protease-sensitive prionopathy.*Definite and probable cases.**Per million inhabitants per annum.
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Demographic characteristics of patients with genetic CJD (1998–2009), caused by various mutations in PRNP.
2013Co-Authors: Casper Jansen, Piero Parchi, Sabina Capellari, Rosaria Strammiello, Carla A. Ibrahim-verbaas, Maaike Schuur, Patrizia Corrado, Matthew T. Bishop, Willem A. Van Gool, Marcel M. VerbeekAbstract:All Ins = insertion; bp = base pairs; M = methionine; V = valine; n.d. = not determined;CJD patients with the same mutation belong to the same family. = Creutzfeldt-Jakob disease; GSS = Gerstmann-Sträussler-Scheinker disease; FFI = Fatal Familial Insomnia; PrP-CAA = prion protein cerebral amyloid angiopathy.
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genetic creutzfeldt jakob disease and Fatal Familial Insomnia insights into phenotypic variability and disease pathogenesis
Acta Neuropathologica, 2011Co-Authors: Sabina Capellari, Rosaria Strammiello, Daniela Saverioni, Hans A Kretzschmar, Piero ParchiAbstract:Human prion diseases are a group of rare neurodegenerative disorders characterized by the conversion of the constitutively expressed prion protein, PrPC, into an abnormally aggregated isoform, called PrPSc. While most people who develop a prion disease have no identifiable cause and a few acquire the disease through an identified source of infection, about 10–15% of patients are affected by a genetic form and carry either a point mutation or an insertion of octapeptide repeats in the prion protein gene. Prion diseases show the highest extent of phenotypic heterogeneity among neurodegenerative disorders and comprise three major disease entities with variable though overlapping phenotypic features: Creutzfeldt–Jakob disease (CJD), Fatal Insomnia and the Gerstmann–Straussler–Scheinker syndrome. Both CJD and Fatal Insomnia are fully transmissible diseases, a feature that led to the isolation and characterization of different strains of the agent or prion showing distinctive clinical and neuropathological features after transmission to syngenic animals. Here, we review the current knowledge of the effects of the pathogenic mutations linked to genetic CJD and Fatal Familial Insomnia on the prion protein metabolism and physicochemical properties, the disease phenotype and the strain characteristics. The data derived from studies in vitro and from those using cell and animal models are compared with those obtained from the analyses of the naturally occurring disease. The extent of phenotypic variation in genetic prion disease is analyzed in comparison to that of the sporadic disease, which has recently been the topic of a systematic and detailed characterization.
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evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity
Science, 1996Co-Authors: Glenn C Telling, Pasquale Montagna, James A Mastrianni, Stephen J Dearmond, Pietro Cortelli, Piero Parchi, E Lugaresi, Pierluigi Gambetti, Ruth Gabizon, Stanley B PrusinerAbstract:The fundamental event in prion diseases seems to be a conformational change in cellular prion protein (PrP C ) whereby it is converted into the pathologic isoform PrP Sc . In Fatal Familial Insomnia (FFI), the protease-resistant fragment of PrP Sc after deglycosylation has a size of 19 kilodaltons, whereas that from other inherited and sporadic prion diseases is 21 kilodaltons. Extracts from the brains of FFI patients transmitted disease to transgenic mice expressing a chimeric human-mouse PrP gene about 200 days after inoculation and induced formation of the 19-kilodalton PrP Sc fragment, whereas extracts from the brains of Familial and sporadic Creutzfeldt-Jakob disease patients produced the 21-kilodalton PrP Sc fragment in these mice. The results presented indicate that the conformation of PrP Sc functions as a template in directing the formation of nascent PrP Sc and suggest a mechanism to explain strains of prions where diversity is encrypted in the conformation of PrP Sc .
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Fatal Familial Insomnia and Familial creutzfeldt jakob disease different prion proteins determined by a dna polymorphism
Proceedings of the National Academy of Sciences of the United States of America, 1994Co-Authors: L Monari, Pasquale Montagna, Robert B Petersen, Pietro Cortelli, Piero Parchi, Shu G Chen, P Brown, Jacqueline Mikol, F Gray, Bernardino GhettiAbstract:Abstract Fatal Familial Insomnia and a subtype of Creutzfeldt-Jakob disease, two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asp-178-->Asn) but segregate with different genotypes determined by this mutation and the methionine-valine polymorphism at codon 129 of the prion protein gene. The abnormal isoforms of the prion protein in these two diseases were found to differ both in the relative abundance of glycosylated forms and in the size of the protease-resistant fragments. The size difference was consistent with a different protease cleavage site, suggesting a different conformation of the protease-resistant prion protein present in the two diseases. These differences are likely to be responsible for the type and location of the lesions that characterize these two diseases. Therefore, the combination of the mutation at codon 178 and the polymorphism at codon 129 determines the disease phenotype by producing two altered conformations of the prion protein.
Jesus R Requena - One of the best experts on this subject based on the ideXlab platform.
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PrPSc Prions: State of the Art
MDPI - Multidisciplinary Digital Publishing Institute, 2018Co-Authors: Joaquín Castilla, Jesus R RequenaAbstract:Prion diseases, or transmissible spongiform encephalopathies (TSEs), are a group of Fatal and transmissible neurodegenerative disorders characterized by long incubation periods, misfolded prion protein (PrP) deposition, and usually spongiform vacuolation. These devastating diseases affect many mammals, with the best known examples being Creutzfeldt–Jakob disease (CJD), Fatal Familial Insomnia (FFI), or Kuru in humans; and scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and chronic wasting disease (CWD) in cervids. Despite major achievements in research of TSEs, there are still many unresolved key issues that hamper the development of effective therapies. However, the last decade has been particularly prolific in advances in the prion field. Among others, prion propagation in vitro has been achieved, leading to new diagnostic methods; the basic architecture of infectious prions has been deciphered; new prion disease types have been described in humans and other animals; and prion disorders have emerged in places that had not previously reported the disorders, as is the case for CWD in Europe.This Special Issue will focus on the state of the art of our knowledge of PrPSc: on what we know about its structure and propagation, the basis of strains and transmission barriers, the mechanisms of PrPSc toxicity, the possible function of PrPSc’s properly folded precursor, PrPC and its evolutionary history, and recent technical breakthroughs in diagnostics and therapy development among other key aspects of PrPSc prion biology
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generation of a new infectious recombinant prion a model to understand gerstmann straussler scheinker syndrome
Scientific Reports, 2017Co-Authors: Saioa R Elezgarai, Natalia Fernandezborges, Hasier Erana, Alejandro M Sevillano, Jorge M Charco, Chafik Harrathi, Paula Saa, David Gil, Qingzhong Kong, Jesus R RequenaAbstract:Human transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of Fatal neurodegenerative disorders that include Kuru, Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome (GSS), and Fatal Familial Insomnia. GSS is a genetically determined TSE caused by a range of mutations within the prion protein (PrP) gene. Several animal models, based on the expression of PrPs carrying mutations analogous to human heritable prion diseases, support that mutations might predispose PrP to spontaneously misfold. An adapted Protein Misfolding Cyclic Amplification methodology based on the use of human recombinant PrP (recPMCA) generated different self-propagating misfolded proteins spontaneously. These were characterized biochemically and structurally, and the one partially sharing some of the GSS PrPSc molecular features was inoculated into different animal models showing high infectivity. This constitutes an infectious recombinant prion which could be an invaluable model for understanding GSS. Moreover, this study proves the possibility to generate recombinant versions of other human prion diseases that could provide a further understanding on the molecular features of these devastating disorders.
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Generation of a new infectious recombinant prion: a model to understand Gerstmann–Sträussler–Scheinker syndrome
Nature Publishing Group, 2017Co-Authors: Saioa R Elezgarai, Natalia Fernández-borges, Hasier Erana, Alejandro M Sevillano, Jorge M Charco, Chafik Harrathi, Paula Saa, David Gil, Qingzhong Kong, Jesus R RequenaAbstract:Abstract Human transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of Fatal neurodegenerative disorders that include Kuru, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome (GSS), and Fatal Familial Insomnia. GSS is a genetically determined TSE caused by a range of mutations within the prion protein (PrP) gene. Several animal models, based on the expression of PrPs carrying mutations analogous to human heritable prion diseases, support that mutations might predispose PrP to spontaneously misfold. An adapted Protein Misfolding Cyclic Amplification methodology based on the use of human recombinant PrP (recPMCA) generated different self-propagating misfolded proteins spontaneously. These were characterized biochemically and structurally, and the one partially sharing some of the GSS PrPSc molecular features was inoculated into different animal models showing high infectivity. This constitutes an infectious recombinant prion which could be an invaluable model for understanding GSS. Moreover, this study proves the possibility to generate recombinant versions of other human prion diseases that could provide a further understanding on the molecular features of these devastating disorders
Pasquale Montagna - One of the best experts on this subject based on the ideXlab platform.
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LETTERS Alteration of the Serotoninergic System in Fatal Familial Insomnia
2013Co-Authors: Pietro Cortelli, Pasquale Montagna, Ronald Polinsky, Elio LugaresiAbstract:We read with interest that Wanschitz and colleagues 1 found a substantial increase in tryptophan hydroxylase-immunoreactive neurons in the pons (superior central nucleus) and medulla (raphe obscurus nucleus) of Fatal Familial Insomnia (FFI) patients, suggesting that a serotoninergic system impairment represents the functional substrate of some typical FFI symptoms. We report the lumbar cerebrospinal fluid (CSF) concentrations of monoamine metabolites in 3 FFI subjects (1 female) of 2 unrelated Italian families already described. 2 We measured 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) by a gas chromatographic, mass spectroscopic method previously described. 3,4 The central component of MHPG was calculated according to the formula [total CSF MHPG] � 0.9 [free plasma MHPG]. 4 FFI patients had the typical poin
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Oneiric stupor: the peculiar behaviour of agrypnia excitata.
Sleep Medicine, 2011Co-Authors: Pietro Guaraldi, Pasquale Montagna, Elio Lugaresi, Pietro Cortelli, Paolo Tinuper, Giovanna Calandra-buonaura, Rossana Terlizzi, Federica ProviniAbstract:Agrypnia excitata (AE) is a syndrome characterized by the inability to sleep associated with a generalized motor and autonomic over-activation. AE is caused by a thalamo-limbic system dysfunction and comprises three different conditions: Fatal Familial Insomnia (FFI), Delirium Tremens (DT), and Morvan Syndrome (MS). Oneiric Stupor episodes (OS) are the peculiar motor behaviour of AE. During OS patients perform simple automatic gestures mimicking daily-life activities. This paper is the first description of the different characteristics of OS in two patients with MS and another with FFI, emphasizing the specific clinical features that reliably differentiate OS from REM sleep behaviour disorders.
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Polysomnographic study of sleeplessness and oneiricisms in the alcohol withdrawal syndrome
Sleep Medicine, 2002Co-Authors: Giuseppe Plazzi, Stefano Meletti, Pasquale Montagna, Elio LugaresiAbstract:Abstract We describe a polysomnographic observation of the acute phase of the alcohol withdrawal syndrome, characterized by an alteration of the sleep–wake cycle and by the absence of non-rapid eye movement sleep. An atypical transitional state between rapid eye movement sleep and wake with hallucinations and enacting-dream behaviors represented the sole sleep pattern. Analogies of alcohol withdrawal syndrome with Fatal Familial Insomnia and Morvan's fibrillary chorea suggest a common pathophysiological mechanism in these conditions.
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evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity
Science, 1996Co-Authors: Glenn C Telling, Pasquale Montagna, James A Mastrianni, Stephen J Dearmond, Pietro Cortelli, Piero Parchi, E Lugaresi, Pierluigi Gambetti, Ruth Gabizon, Stanley B PrusinerAbstract:The fundamental event in prion diseases seems to be a conformational change in cellular prion protein (PrP C ) whereby it is converted into the pathologic isoform PrP Sc . In Fatal Familial Insomnia (FFI), the protease-resistant fragment of PrP Sc after deglycosylation has a size of 19 kilodaltons, whereas that from other inherited and sporadic prion diseases is 21 kilodaltons. Extracts from the brains of FFI patients transmitted disease to transgenic mice expressing a chimeric human-mouse PrP gene about 200 days after inoculation and induced formation of the 19-kilodalton PrP Sc fragment, whereas extracts from the brains of Familial and sporadic Creutzfeldt-Jakob disease patients produced the 21-kilodalton PrP Sc fragment in these mice. The results presented indicate that the conformation of PrP Sc functions as a template in directing the formation of nascent PrP Sc and suggest a mechanism to explain strains of prions where diversity is encrypted in the conformation of PrP Sc .
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Fatal Familial Insomnia and Familial creutzfeldt jakob disease different prion proteins determined by a dna polymorphism
Proceedings of the National Academy of Sciences of the United States of America, 1994Co-Authors: L Monari, Pasquale Montagna, Robert B Petersen, Pietro Cortelli, Piero Parchi, Shu G Chen, P Brown, Jacqueline Mikol, F Gray, Bernardino GhettiAbstract:Abstract Fatal Familial Insomnia and a subtype of Creutzfeldt-Jakob disease, two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asp-178-->Asn) but segregate with different genotypes determined by this mutation and the methionine-valine polymorphism at codon 129 of the prion protein gene. The abnormal isoforms of the prion protein in these two diseases were found to differ both in the relative abundance of glycosylated forms and in the size of the protease-resistant fragments. The size difference was consistent with a different protease cleavage site, suggesting a different conformation of the protease-resistant prion protein present in the two diseases. These differences are likely to be responsible for the type and location of the lesions that characterize these two diseases. Therefore, the combination of the mutation at codon 178 and the polymorphism at codon 129 determines the disease phenotype by producing two altered conformations of the prion protein.
Herbert Budka - One of the best experts on this subject based on the ideXlab platform.
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predictors of survival in sporadic creutzfeldt jakob disease and other human transmissible spongiform encephalopathies
Brain, 2004Co-Authors: Maurizio Pocchiari, Steven J Collins, Maria Puopolo, Esther A Croes, Herbert Budka, Ellen Gelpi, Victoria Lewis, T Sutcliffe, A Guilivi, N DelasnerielaupretreAbstract:A collaborative study of human transmissible spongiform encephalopathies has been carried out from 1993 to 2000 and includes data from 10 national registries, the majority in Western Europe. In this study, we present analyses of predictors of survival in sporadic (n = 2304), iatrogenic (n = 106) and variant Creutzfeldt-Jakob disease (n = 86) and in cases associated with mutations of the prion protein gene (n = 278), including Gerstmann-Straussler-Scheinker syndrome (n = 24) and Fatal Familial Insomnia (n = 41). Overall survival for each disease type was assessed by the Kaplan-Meier method and the multivariate analyses by the Cox proportional hazards model. In sporadic disease, longer survival was correlated with younger age at onset of illness, female gender, codon 129 heterozygosity, presence of CSF 14-3-3 protein and type 2a prion protein type. The ability to predict survival based on patient covariates is important for diagnosis and counselling, and the characterization of the survival distributions, in the absence of therapy, will be an important starting point for the assessment of potential therapeutic agents in the future.
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disease associated prion protein may deposit in the peripheral nervous system in human transmissible spongiform encephalopathies
Acta Neuropathologica, 1999Co-Authors: Johannes A Hainfellner, Herbert BudkaAbstract:There is increasing evidence indicating involvement of the peripheral nervous system (PNS) in the pathogenesis of transmissible spongiform encephalopathies (TSEs). Immunocytochemically detectable deposits of TSE-specific abnormal prion protein (PrPsc) are considered as a surrogate marker for infectivity. We used anti-PrP immunocytochemistry to trace PrPsc deposition in spinal and enteric ganglia, and peripheral nerve in Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease (GSS), and Fatal Familial Insomnia. Discrete PrPsc deposits were detectable only in a few posterior root nerve fibers in an adaxonal location in one of nine CJD and the one GSS patients examined. Follicular dendritic cells of the gut and enteric nervous system were not labeled. Thus, PrPsc may spread to the PNS in different forms of human prion disease. In contrast to our observations in experimental scrapie (Groschup et al., Acta Neuropathol, this issue), the deposits were scant. Possible explanations for this discrepancy comprise strain difference, or centripetal (experimental scrapie) versus centrifugal (sporadic and genetic human prion diseases) spread of PrPsc, resulting in different patterns and amounts of PrPsc accumulation in the PNS.