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The term Prion means 'infectious protein' in any organism, irrespective of the mechanism and implies the absence of a nuclei acid necessary for the infectivity. Infectious proteins (Prion) include the transmissible spongiform encephalopathies (TSES) of mammals, the amyloidoses [URE3], [PSI] and [PIN] of Saccharomyces cerevisiac, [Het-s] of the filamentous fungus podospora anserina, and the self-activating in trans vocular protease B of yeast.

Posttranslational modifications are a common feature of proteins associated with neurodegenerative diseases including prion protein ([PrP.sup.C]), tau, and a-synuclein. Alternative self-propagating protein states or strains give rise to different disease phenotypes and display strain-specific subsets of posttranslational modifications. The relationships between strain-specific structure, posttranslational modifications, and disease phenotype are poorly understood. We previously reported that among hundreds of [PrP.sup.C] sialoglycoforms expressed by a cell, individual prion strains recruited [PrP.sup.C] molecules selectively, according to the sialylation status of their N-linked glycans. Here we report that transmission of a prion strain to a new host is accompanied by a dramatic shift in the selectivity of recruitment of [PrP.sup.C] sialoglycoforms, giving rise to a self-propagating scrapie isoform ([PrP.sup.Sc]) with a unique sialoglycoform signature and disease phenotype. The newly emerged strain has the shortest incubation time to disease and is characterized by colocalization of [PrP.sup.Sc] with microglia and a very profound proinflammatory response, features that are linked to a unique sialoglycoform composition of [PrP.sup.Sc]. The current work provides experimental support for the hypothesis that strain-specific patterns of [PrP.sup.Sc] sialoglycoforms formed as a result of selective recruitment dictate strain-specific disease phenotypes. This work suggests a causative relationship between a strain-specific structure, posttranslational modifications, and disease phenotype., Introduction Prion diseases are a group of fatal neurodegenerative diseases of humans and other mammals that can arise spontaneously or via transmission (1). The transmissible agent of prion disease consists [...]

In 2016, a definite case of clinical variant Creutzfeldt-Jakob disease (vCJD) in a person heterozygous for methionine/valine (MV) at codon 129 of the prion protein gene (PRNP 129MV) was reported [...]

Prion diseases are fatal, transmissible neurodegenerative disorders characterized by deposition of abnormal prion protein ([PrP.sup.Sc]) in the brain (1). Human prion diseases, which include Creutzfeldt-Jakob disease (CJD), are classified into [...]

Prion diseases, or transmissible spongiform encephalopathies (TSEs), are a group of rare and lethal neurodegenerative diseases that affect a great number of mammal species, including humans and animals belonging to [...]

Sporadic prion diseases are classified according to phenotype as well as the pairing of the prion protein (PrP) genotype at the methionine (M)/valine (V) polymorphic codon 129 and the conformational [...]

Heparin is a widely used injectable anticoagulant. In the 1990s, bovine-derived heparin was withdrawn from the US market because of concerns about possible contamination of bovine tissues with the agent [...]

The prion agent is unique in biology and is comprised of prion protein scrapie ([PrP.sup.Sc]), a self-templating conformational variant of the host encoded prion protein cellular ([PrP.sup.C]). The deposition patterns of [PrP.sup.Sc] in the CNS can vary considerably from a diffuse synaptic pattern to large plaque-like aggregates. Alterations of [PrP.sup.C] posttranslational processing can change [PrP.sup.Sc] deposition patterns; however, the mechanism underlying these observations is unclear. In this issue of the JCI, Sevillano and authors determined that parenchymal [PrP.sup.Sc] plaques of the mouse brain preferentially incorporated underglycosylated [PrP.sup.C] that had been liberated from the cell surface by the metalloproteinase, ADAM-10, in combination with heparan sulfate. These results provide mechanistic insight into the formation of [PrP.sup.Sc] plaques and suggest that PrP posttranslational modifications direct pathogenicity as well as the rate of disease progression., Protein-only infectious agents Prions are protein-only infectious agents that subvert the normal form of the host cellular prion protein, [PrP.sup.C], to the self-templating scrapie prion form, [PrP.sup.Sc] (1, 2). Due [...]

The presence of variant Creutzfeldt-Jakob disease (vCJD) is considered by strong epidemiologic, pathologic, and molecular evidence to be a likely consequence of human dietary exposure to the bovine spongiform encephalopathy [...]

Prions are notorious protein-only infectious agents that cause invariably fatal brain diseases following silent incubation periods that can span a lifetime. These diseases can arise spontaneously, through infection or be inherited. Remarkably, prions are composed of self-propagating assemblies of a misfolded cellular protein that encode information, generate neurotoxicity and evolve and adapt in vivo. Although parallels have been drawn with Alzheimer's disease and other neurodegenerative conditions involving the deposition of assemblies of misfolded proteins in the brain, insights are now being provided into the usefulness and limitations of prion analogies and their aetiological and therapeutic relevance., Author(s): John Collinge (corresponding author) [1, 2] Prions are lethal pathogenic agents that cause neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and goats, transmissible mink [...]

Byline: Parmenides. Guadarrama-Ortiz, Jose. Choreno-Parra, Martha. Carnalla-Cortes, Patricia. Rodriguez-Munoz, Manuel. Angeles-Castellanos Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal and rapidly progressive form of dementia caused by the spread of a [...]

Author(s): Simon Makin [1] [illus. 1] It was a meeting that they would never forget. Patrik Brundin and Anders Björklund, two Swedish neuroscientists, were attending a symposium at Stockholm's Karolinska [...]

Author(s): Alexander Kffer [1]; Asvin K. K. Lakkaraju [1]; Amit Mogha [2]; Sarah C. Petersen [2]; Kristina Airich [1]; Cdric Doucerain [1]; Rajlakshmi Marpakwar [1]; Pamela Bakirci [1]; Assunta Senatore [...]