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1.
Laura Solforosi Michela Milani Nicasio Mancini Massimo Clementi Roberto Burioni 《朊病毒》2013,7(2):99-108
Prions are infectious proteins that are responsible for transmissible spongiform encephalopathies (TSEs) and consist primarily of scrapie prion protein (PrPSc), a pathogenic isoform of the host-encoded cellular prion protein (PrPC). The absence of nucleic acids as essential components of the infectious prions is the most striking feature associated to these diseases. Additionally, different prion strains have been isolated from animal diseases despite the lack of DNA or RNA molecules. Mounting evidence suggests that prion-strain-specific features segregate with different PrPSc conformational and aggregation states. Strains are of practical relevance in prion diseases as they can drastically differ in many aspects, such as incubation period, PrPSc biochemical profile (e.g., electrophoretic mobility and glycoform ratio) and distribution of brain lesions. Importantly, such different features are maintained after inoculation of a prion strain into genetically identical hosts and are relatively stable across serial passages. This review focuses on the characterization of prion strains and on the wide range of important implications that the study of prion strains involves. 相似文献
2.
Highly Infectious CJD Particles Lack Prion Protein but Contain Many Viral‐Linked Peptides by LC‐MS/MS 下载免费PDF全文
Terry Kipkorir Sarah Tittman Sotirios Botsios Laura Manuelidis 《Journal of cellular biochemistry》2014,115(11):2012-2021
3.
Edward Málaga-Trillo Evgenia Salta Antonio FiguerasCynthia Panagiotidis Theodoros Sklaviadis 《生物化学与生物物理学报:疾病的分子基础》2011,1812(3):402-414
Transmissible spongiform encephalopathies (TSEs), otherwise known as prion disorders, are fatal diseases causing neurodegeneration in a wide range of mammalian hosts, including humans. The causative agents - prions - are thought to be composed of a rogue isoform of the endogenous prion protein (PrP). Beyond these and other basic concepts, fundamental questions in prion biology remain unanswered, such as the physiological function of PrP, the molecular mechanisms underlying prion pathogenesis, and the origin of prions. To date, the occurrence of TSEs in lower vertebrates like fish and birds has received only limited attention, despite the fact that these animals possess bona fide PrPs. Recent findings, however, have brought fish before the footlights of prion research. Fish models are beginning to provide useful insights into the roles of PrP in health and disease, as well as the potential risk of prion transmission between fish and mammals. Although still in its infancy, the use of fish models in TSE research could significantly improve our basic understanding of prion diseases, and also help anticipate risks to public health. This article is part of a Special Issue entitled Zebrafish Models of Neurological Diseases. 相似文献
4.
Nani Van Gerven Sander E. Van der Verren Dirk M. Reiter Han Remaut 《Journal of molecular biology》2018,430(20):3657-3684
Amyloid fibrils are best known as a product of human and animal protein misfolding disorders, where amyloid formation is associated with cytotoxicity and disease. It is now evident that for some proteins, the amyloid state constitutes the native structure and serves a functional role. These functional amyloids are proving widespread in bacteria and fungi, fulfilling diverse functions as structural components in biofilms or spore coats, as toxins and surface-active fibers, as epigenetic material, peptide reservoirs or adhesins mediating binding to and internalization into host cells. In this review, we will focus on the role of functional amyloids in bacterial pathogenesis. The role of functional amyloids as virulence factor is diverse but mostly indirect. Nevertheless, functional amyloid pathways deserve consideration for the acute and long-term effects of the infectious disease process and may form valid antimicrobial targets. 相似文献
5.
Franco Cardone Serena Principe Maria Eugenia Schininà Bruno Maras Sabina Capellari Piero Parchi Silvio Notari Laura Di Francesco Anna Poleggi Roberta Galeno Ramona Vinci Vittorio Mellina Susanna Almonti Anna Ladogana Maurizio Pocchiari 《Biochemical and biophysical research communications》2014
Creutzfeldt–Jakob disease (CJD) is a neurodegenerative disorder characterized by the deposition of the pathological conformer (PrPCJD) of the host encoded cellular prion protein (PrPC). In genetic CJD associated with V210I or R208H PrP substitutions, the pathogenic role of mutant residues is still poorly understood. To understand how V210I or R208H PrP mutations facilitate the development of the disease, we determined by mass spectrometry the quantitative ratio of mutant/wild-type PrPCJD allotypes in brains from affected subjects. We found that the mutant PrPCJD allotypes moderately exceeds of 2- or 3-fold the amount of the wild-type counterpart suggesting that these mutations mainly exert their pathogenic effect on the onset of the pathogenic cascade. 相似文献
6.
为了探讨蛋白激酶CK2与PrP是否存在分子间相互作用,利用RT-PCR方法从人源细胞系SH-SY5Y cDNA中分别扩增出蛋白激酶CK2a和CK2β基因,并在E coli中表达了融合蛋白HIS-CK2α和GST-HISCK2β.利用pU-doWn及免疫共沉淀实验检测PrP与CK2的分子间相互作用.结果显示,重组PrP可与CK2α出现特异性结合,但不与CK2β发生反应.天然状态下脑组织中的CK2与PrPc也发生相互作用.PrP与CK2α亚基相互作用的区域位于PrP的C-端90~231位氨基酸.本研究从分子水平上提供了人重组和天然CK2和PrP蛋白相互作用的实验依据,为深入探讨CK2与朊蛋白作用的生物学意义和在朊病毒病发病过程中的作用提供了科学线索. 相似文献
7.
Mohammad Farooque Hassan Sher Hayat Khan Masroor Ellahi Babar Lifeng Yang Tariq Ali Jamal Muhammad Khan 《朊病毒》2016,10(4):290-304
The association between caprine PrP gene polymorphisms and its susceptibility to scrapie has been investigated in current years. As the ORF of the PrP gene is extremely erratic in different breeds of goats, we studied the PrP gene polymorphisms in 80 goats which belong to 11 Pakistani indigenous goat breeds from all provinces of Pakistan. A total of 6 distinct polymorphic sites (one novel) with amino acid substitutions were identified in the PrP gene which includes 126 (A -> G), 304 (G -> T), 379 (A -> G), 414 (C -> T), 428 (A -> G) and 718 (C -> T). The locus c.428 was found highly polymorphic in all breeds as compare to other loci. On the basis of these PrP variants NJ phylogenetic tree was constructed through MEGA6.1 which showed that all goat breeds along with domestic sheep and Mauflon sheep appeared as in one clade and sharing its most recent common ancestors (MRCA) with deer species while Protein analysis has shown that these polymorphisms can lead to varied primary, secondary and tertiary structure of protein. Based on these polymorphic variants, genetic distance, multidimensional scaling plot and principal component analyses revealed the clear picture regarding greater number of substitutions in cattle PrP regions as compared to the small ruminant species. In particular these findings may pinpoint the fundamental control over the scrapie in Capra hircus on genetic basis. 相似文献
8.
Katarzyna M. OsieckaHanna Nieznanska Krzysztof J. SkowronekJolanta Jozwiak Krzysztof Nieznanski 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2011,1813(10):1845-1853
In previous studies we have demonstrated that prion protein (PrP) interacts with tubulin and disrupts microtubular cytoskeleton by inducing tubulin oligomerization. These observations may explain the molecular mechanism of toxicity of cytoplasmic PrP in transmissible spongiform encephalopathies (TSEs). Here, we check whether microtubule associated proteins (MAPs) that regulate microtubule stability, influence the PrP-induced oligomerization of tubulin. We show that tubulin preparations depleted of MAPs are more prone to oligomerization by PrP than those containing traces of MAPs. Tau protein, a major neuronal member of the MAPs family, reduces the effect of PrP. Importantly, phosphorylation of Tau abolishes its ability to affect the PrP-induced oligomerization of tubulin. We propose that the binding of Tau stabilizes tubulin in a conformation less susceptible to oligomerization by PrP. Since elevated phosphorylation of Tau leading to a loss of its function is observed in Alzheimer disease and related tauopathies, our results point at a possible molecular link between these neurodegenerative disorders and TSEs. 相似文献
9.
Paulis D Maras B Schininà ME di Francesco L Principe S Galeno R Abdel-Haq H Cardone F Florio T Pocchiari M Mazzanti M 《Neurochemistry international》2011,59(2):168-174
Transmissible spongiform encephalopathies (TSEs) are neurodegenerative pathologies characterized by the accumulation of amyloid fibrils mainly composed of the pathological isoform of the prion protein (PrPTSE). PrPTSE pre-amyloid fibrils are supposed to induce neurodegenerative lesions possibly through the alteration of membrane permeability. The effect of PrPTSE on cellular membranes has been modeled in vitro by synthetic peptides that are, however, only partially representative of PrPTSE isoforms found in vivo. In the present work we show that a synthetic membrane exposed to PrP27-30 extracted from TSE-infected hamster brains changes its permeability because of the formation of molecular pores that alter the conductance of the synthetic lipid bilayer. Synthetic membrane challenged with the recombinant prion peptide PrP90-231 shows a much lower conductance. Elevation of calcium ion concentration not only increases the current amplitude due to the action of both PrP27-30 and PrP90-231 on the membrane, but also amplifies the interaction of PrP90-231 with the lipid bilayer. 相似文献
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