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Прионы и прионские заболевания: Понимание с глаз.

Болезни приона всегда являются смертельными нейродегенеративными расстройствами, которые получили широкую огласку из-за их трансмиссии. Болезнь Спорадик Креуцфельдта-Якоба (SCJD) является наиболее распространенным заболеванием приона человека с частотой 1 к миллиону. Наследственные прионные расстройства относительно редки и связаны с мутациями в гене приона. До настоящего времени было выявлено более 50 различных мутаций, исключений и вложений. Большинство из них доминируют в автосомии и полностью проникают в организм. Прионские расстройства также встречаются у животных и вызывают серьезную оза

Treatment of Prion Disease with Heterologous Prion Proteins.

Prion diseases such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, and scrapie in sheep are fatal neurodegenerative diseases for which there is no effective treatment. The pathology of these diseases involves the conversion of a protease sensitive form of the cellular prion protein (PrPC) into a protease resistant infectious form (PrPsc or PrPres). Both in vitro (cell culture and cell free conversion assays) and in vivo (animal) studies have demonstrated the strong dependence of this conversion process on protein sequence homology between the initial prion

Prions and prion diseases: fundamentals and mechanistic details.

Prion diseases, often called transmissible spongiform encephalopathies (TSEs), are infectious diseases that accompany neurological dysfuncti … certain species but can be transmissible from one host species to another. Such a striking nature ofprions has generated huge concerns in public health and attracted serious attention in the scientific communities. To date, the potential transmission ofprions to humans via foodbome infectiorn and iatrogenic routes has not been alleviated. Rather, the pos …

Prion protein transgenes and the neuropathology in prion diseases.

The concept that prions are novel pathogens which are different from both viroids and viruses has received increasing support from many avenues of investigation over the past decade. Enriching fractions from Syrian hamster (SHa) brain for scrapie prion infectivity led to the discovery of the prion protein (PrP). Prion diseases of animals include scrapie and "mad cow" disease; those of humans present as inherited, sporadic and infectious neurodegenerative disorders, two of which are called Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker disease (GSS). The inherited human prio…

Yeast Prions: Discovery, Nature, Cellular Manipulation and Implication.

Prion is simply an infectious protein, and it occurs spontaneously without any well-defined reason. Once prions occurred, they mostly propagated in biophysically very stable amyloid form with self-templating mechanism. Human and mammalian prion results in untreatable and even fatal brain disorders, thus study of prion and its pathology extremely difficult. However, since the first discovery of two prions in model microorganism Saccharomyces cerevisiae, studies about prion biology, host physiology affected by prion or prion disease have facilitated. Moreover, many attempts to understand human a…

Extracellular Vesicles and the Propagation of Yeast Prions.

Infectious proteins or prions are self-replicating transmissible aggregates responsible for heritable traits in yeasts and amyloid diseases in mammals. Extensive investigations into the many prions discovered in the yeast Saccharomyces cerevisiae, and most importantly the [PSI+] prion, shaped our understanding of the cellular mechanisms involved in amyloidosis. [PSI+] arises from the assembly of the translation terminator Sup35p into insoluble fibrillar aggregates leading to nonsense suppression phenotypes. We recently found that infectious Sup35p particles traffic via extracellular (EV) and p…

Prions activate a p38 MAPK synaptotoxic signaling pathway.

Synaptic degeneration is one of the earliest pathological correlates of prion disease, and it is a major determinant of the progression of clinical symptoms. However, the cellular and molecular mechanisms underlying prion synaptotoxicity are poorly understood. Previously, we described an experimental system in which treatment of cultured hippocampal neurons with purified PrPSc, the infectious form of the prion protein, induces rapid retraction of dendritic spines, an effect that is entirely dependent on expression of endogenous PrPC by the target neurons. Here, we use this system to dissect ph

Искусственный штамм человеческих прионов, созданных in vitro.

Молекулярный механизм, определяющий в физиологических условиях способность к переносу наиболее часто встречающейся болезни приона человека, спорадической болезни Креуцфельдта-Якоба (SCJD), неизвестен. Мы сообщаем об синтезе нового человеческого приона из рекомбинированного человеческого белка приона, выраженного в бактериях в реакции, посеянных SCJD MM1 прионами и кофактором, ганглиозадным GM1. Эти синтетические человеческие прионы были заразны трансгенными мышами, выражающими негликозилированный человеческий прионный белок, что вызвало неврологическую дисфункцию после 459 и 224 дней в первом

Совпадение в аннотации оригинала
The molecular mechanism that determines under physiological conditions transmissibility of the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD) is unknown. We report the synthesis of new human prion from the recombinant human prion protein expressed in bacteria in reaction seeded with sCJD MM1 prions and cofactor, ganglioside GM1. T…

The Structure of Mammalian Prions and Their Aggregates.

Prion diseases, such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, chronic wasting disease in cervids (i.e., deer, elk, moose, and reindeer), and sheep scrapie, are caused by the misfolding of the cellular prion protein (PrPC) into a disease-causing conformer (PrPSc). PrPC is a normal, GPI-anchored protein that is expressed on the surface of neurons and other cell types. The structure of PrPC is well understood, based on studies of recombinant PrP, which closely mimics the structure of native PrPC. In contrast, PrPSc is prone to aggregate into a variety of

Prions in variably protease-sensitive prionopathy: an update.

Human prion diseases, including sporadic, familial, and acquired forms such as Creutzfeldt-Jakob disease (CJD), are caused by prions in which an abnormal prion protein (PrPSc) derived from its normal cellular isoform (PrPC) is the only known component. The recently-identified variably protease-sensitive prionopathy (VPSPr) is characterized not only by an atypical clinical phenotype and neuropathology but also by the deposition in the brain of a peculiar PrPSc. Like other forms of human prion disease, the pathogenesis of VPSPr also currently remains unclear. However, the findings of the peculia…

Прионы, чувствительные к протеинам, с мутации вращения 144-bp.

Включение 144-базовой пары (bp), содержащей шесть дополнительных октапептидных повторов между остатками 51 и 91 прионного белка (PrP), связано с унаследованными прионными заболеваниями. В большинстве случаев, связанных с этим включением, которое было изучено Western Blotting, было выявлено наличие обнаруживаемой стойкости к протеиназе K PrPSc (rPRPSc), которая напоминает тип 1 и тип 2 в эпизодической болезни Crewzfeldt-Jakob (SCJD), или PrP7-8 в болезни Герстманн-Sträussler-Scheinder. Вместе с тем были также получены сообщения о случаях, в которых отсутствует возможность обнаружения ПРПСc. Кто

Emergence and natural selection of drug-resistant prions.

Drug resistance is a refractory barrier in the battle against many fatal diseases caused by rapidly evolving agents, including HIV, apicomplexans and specific cancers. Emerging evidence suggests that drug resistance might extend to lethal prion disorders and related neurodegenerative amyloidoses. Prions are self-replicating protein conformers, usually 'cross-beta' amyloid polymers, which are naturally transmitted between individuals and promote phenotypic change. Prion conformers are catalytic templates that specifically convert other copies of the same protein to the prion form. Once in motio…

[Biology of non-conventional transmissible agents or prions].

Transmissible subacute spongiform encephalopathies (TSE) are a group of human and animal diseases which includes Creutzfeldt-Jakob disease, … nlike other micro-organisms; they are known as transmissible spongiform encephalopathy agent (TSA), prions, or virinos. So far, despite considerable progress made in the molecular biology toward the understanding of neurological injury, the nature of the TSA/prions remains unknown. TSE are characterised by the pathognomic accumulation, within the central …

Prion protein scrapie and the normal cellular prion protein.

Prions are infectious proteins and over the past few decades, some prions have become renowned for their causative role in several neurodegenerative diseases in animals and humans. Since their discovery, the mechanisms and mode of transmission and molecular structure of prions have begun to be established. There is, however, still much to be elucidated about prion diseases, including the development of potential therapeutic strategies for treatment. The significance of prion disease is discussed here, including the categories of human and animal prion diseases, disease transmission, disease pr…

Ticks harbor and excrete chronic wasting disease prions.

Chronic wasting disease (CWD) is a fatal neurodegenerative disease caused by infectious prions (PrPCWD) affecting cervids. Circulating PrPCWD in blood may pose a risk for indirect transmission by way of hematophagous ectoparasites acting as mechanical vectors. Cervids can carry high tick infestations and exhibit allogrooming, a common tick defense strategy between conspecifics. Ingestion of ticks during allogrooming may expose naïve animals to CWD, if ticks harbor PrPCWD. This study investigates whether ticks can harbor transmission-relevant quantities of PrPCWD by combining experimental tick …

Biodegradation of bovine spongiform encephalopathy prions in compost.

To reduce the transmission risk of bovine spongiform encephalopathy prions (PrPBSE), specified risk materials (SRM) that can harbour PrPBSE are prevented from entering the feed and food chains. As composting is one approach to disposing of SRM, we investigated the inactivation of PrPBSE in lab-scale composters over 28 days and in bin composters over 106-120 days. Lab-scale composting was conducted using 45 kg of feedlot manure with and without chicken feathers. Based on protein misfolding cyclic amplification (PMCA), after 28 days of composting, PrPBSE seeding activity was reduced by 3-4 log10…

Generation of novel neuroinvasive prions following intravenous challenge.

Prions typically spread into the central nervous system (CNS), likely via peripheral nerves. Yet prion conformers differ in their capacity to penetrate the CNS; certain fibrillar prions replicate persistently in lymphoid tissues with no CNS entry, leading to chronic silent carriers. Subclinical carriers of variant Creutzfeldt-Jakob (vCJD) prions in the United Kingdom have been estimated at 1:2000, and vCJD prions have been transmitted through blood transfusion, however, the circulating prion conformers that neuroinvade remain unclear. Here we investigate how prion conformation impacts brain en…