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https://www.readbyqxmd.com/read/28428956/physiological-functions-of-the-cellular-prion-protein
#1
REVIEW
Andrew R Castle, Andrew C Gill
The prion protein, PrP(C), is a small, cell-surface glycoprotein notable primarily for its critical role in pathogenesis of the neurodegenerative disorders known as prion diseases. A hallmark of prion diseases is the conversion of PrP(C) into an abnormally folded isoform, which provides a template for further pathogenic conversion of PrP(C), allowing disease to spread from cell to cell and, in some circumstances, to transfer to a new host. In addition to the putative neurotoxicity caused by the misfolded form(s), loss of normal PrP(C) function could be an integral part of the neurodegenerative processes and, consequently, significant research efforts have been directed toward determining the physiological functions of PrP(C)...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28427069/practical-lessons-from-protocol-i-for-the-management-of-diabetic-macular-edema
#2
Lekha Mukkamala, Neelakshi Bhagat, Marco A Zarbin
Protocol I, a multicenter randomized clinical trial, compared the visual outcomes of patients treated with 0.5 mg intravitreal ranibizumab with either prompt or deferred (by 24 weeks laser), 4 mg intravitreal triamcinolone with prompt laser, or sham injection with prompt laser for the treatment of center-involving diabetic macular edema (DME). A total of 854 adult patients with type I or II diabetes and any level of non-proliferative diabetic retinopathy or proliferative retinopathy with adequate panretinal photocoagulation, with best-corrected visual acuity (BCVA) of 78 to 24 ETDRS letters (Snellen equivalent of 20/32 to 20/320) and visual loss attributed to macular edema, or retinal thickening with central subfield thickness of at least 250 µm by OCT were enrolled...
2017: Developments in Ophthalmology
https://www.readbyqxmd.com/read/28421536/lysosomal-quality-control-in-prion-diseases
#3
REVIEW
Priyanka Majumder, Oishee Chakrabarti
Prion diseases are transmissible, familial or sporadic. The prion protein (PrP), a normal cell surface glycoprotein, is ubiquitously expressed throughout the body. While loss of function of PrP does not elicit apparent phenotypes, generation of misfolded forms of the protein or its aberrant metabolic isoforms has been implicated in a number of neurodegenerative disorders such as scrapie, kuru, Creutzfeldt-Jakob disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker and bovine spongiform encephalopathy...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28420443/tau-phosphorylation-induced-by-severe-closed-head-traumatic-brain-injury-is-linked-to-the-cellular-prion-protein
#4
Richard Rubenstein, Binggong Chang, Natalia Grinkina, Eleanor Drummond, Peter Davies, Meir Ruditzky, Deep Sharma, Kevin Wang, Thomas Wisniewski
Studies in vivo and in vitro have suggested that the mechanism underlying Alzheimer's disease (AD) neuropathogenesis is initiated by an interaction between the cellular prion protein (PrP(C)) and amyloid-β oligomers (Aβo). This PrP(C)-Aβo complex activates Fyn kinase which, in turn, hyperphosphorylates tau (P-Tau) resulting in synaptic dysfunction, neuronal loss and cognitive deficits. AD transgenic mice lacking PrP(C) accumulate Aβ, but show normal survival and no loss of spatial learning and memory suggesting that PrP(C) functions downstream of Aβo production but upstream of intracellular toxicity within neurons...
April 18, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28415023/drosophila-models-of-prionopathies-insight-into-prion-protein-function-transmission-and-neurotoxicity
#5
REVIEW
Pedro Fernandez-Funez, Jonatan Sanchez-Garcia, Diego E Rincon-Limas
Prion diseases (PrD) are unique neurodegenerative conditions with sporadic, genetic, and infectious etiologies. The agent responsible for these pathologies is a misfolded conformation of the prion protein (PrP). Although a process of autocatalytic "conversion" is known to mediate disease transmission, important gaps still remain regarding the physiological function of PrP and its relevance to pathogenesis, the molecular and cellular mechanisms mediating neurotoxicity and transmission, and the PrP conformations responsible for neurotoxicity...
April 14, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28413194/dual-role-of-cellular-prion-protein-in-normal-host-and-alzheimer-s-disease
#6
REVIEW
Takashi Onodera
Using PrP(C)-knockout cell lines, it has been shown that the inhibition of apoptosis through STI1 is mediated by PrP(C)-dependent SOD activation. Antioxidant PrP(C) may contribute to suppression of inflammasome activation. PrP(C) is functionally involved in copper metabolism, signal transduction, neuroprotection, and cell maturation. Recently several reports have shown that PrP(C) participates in trans-membrane signaling processes associated with hematopoietic stem cell replication and neuronal differentiation...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28407243/simulations-of-membrane-bound-diglycosylated-human-prion-protein-reveal-potential-protective-mechanisms-against-misfolding
#7
Chin Jung Cheng, Heidi Koldsø, Marc W Van der Kamp, Birgit Schiøtt, Valerie Daggett
Prion diseases are associated with the misfolding of the prion protein (PrP) from its normal cellular form (PrP(C) ) to its infectious scrapie form (PrP(S)(c) ). Posttranslational modifications of PrP in vivo can play an important role in modulating the process of misfolding. To gain more insight into the effects of posttranslational modifications on PrP structure and dynamics and to test the hypothesis that such modifications can interact with the protein, we have performed molecular dynamics simulations of diglycosylated human PrP(C) bound to a lipid bilayer via a glycophosphatidylinositol anchor...
April 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28406520/the-folding-mechanism-and-key-metastable-state-identification-of-the-prp127-147-monomer-studied-by-molecular-dynamics-simulations-and-markov-state-model-analysis
#8
Shuangyan Zhou, Qianqian Wang, Yuwei Wang, Xiaojun Yao, Wei Han, Huanxiang Liu
The structural transition of prion proteins from a native α-helix (PrP(C)) to a misfolded β-sheet-rich conformation (PrP(Sc)) is believed to be the main cause of a number of prion diseases in humans and animals. Understanding the molecular basis of misfolding and aggregation of prion proteins will be valuable for unveiling the etiology of prion diseases. However, due to the limitation of conventional experimental techniques and the heterogeneous property of oligomers, little is known about the molecular architecture of misfolded PrP(Sc) and the mechanism of structural transition from PrP(C) to PrP(Sc)...
April 13, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28357807/dual-microrna-to-cellular-prion-protein-inhibits-propagation-of-pathogenic-prion-protein-in-cultured-cells
#9
Sang-Gyun Kang, Chiye Kim, Judd Aiken, Han Sang Yoo, Debbie McKenzie
Prion diseases are fatal transmissible neurodegenerative disorders affecting humans and various mammals. In spite of intensive efforts, there is no effective cure or treatment for prion diseases. Cellular forms of prion protein (PrP(C)) is essential for propagation of abnormal isoforms of prion protein (PrP(Sc)) and pathogenesis. The effect of an artificial dual microRNA (DmiR) on PrP(C) suppression and resultant inhibition of prion replication was determined using prion-infectible cell cultures: differentiated C2C12 culture and primary mixed neuronal and glial cells culture (MNGC)...
March 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28341267/in-vivo-clinical-and-radiological-effects-of-platelet-rich-plasma-on-interstitial-supraspinatus-lesion-case-series
#10
A Lädermann, M A Zumstein, F C Kolo, M Grosclaude, L Koglin, A J P Schwitzguebel
BACKGROUND: Rotator cuff tear (RCT) is a frequent condition of clinical relevance that can be managed with a symptomatic conservative treatment, but surgery is often needed. Biological components like leukocytes and platelet rich plasma (L-PRP) could represent an alternative curative method for interstitial RCT. HYPOTHESES: It has been hypothesized that an ultrasound guided L-PRP injection in supraspinatus interstitial RCT could induce radiological healing. MATERIAL AND METHODS: A prospective case series including 25 patients was performed in order to assess the effect of L-PRP infiltration into supraspinatus interstitial RCTs...
December 2016: Orthopaedics & Traumatology, Surgery & Research: OTSR
https://www.readbyqxmd.com/read/28324664/limited-understanding-of-the-functional-diversity-of-n-linked-glycans-as-a-major-gap-of-prion-biology
#11
Ilia V Baskakov
Among a broad range of hypotheses on the molecular nature of transmissible spongiform encephalopathy or scrapie agents discussed in 1960s was a hypothesis of self-replicating polysaccharides. While the studies of the past 40 years provided unambiguous proof that this is not the case, emerging evidence suggests that carbohydrates in the form of sialylated N-linked glycans, which are a constitutive part of mammalian prions or PrP(Sc), are essential in determining prion fate in an organism. The current extra-view article discusses recent advancements on the role of N-linked glycans and specifically their sialylation status in controlling prion fate...
March 4, 2017: Prion
https://www.readbyqxmd.com/read/28298604/prion-strain-characterization-of-a-novel-subtype-of-creutzfeldt-jakob-disease
#12
Roberta Galeno, Michele Angelo Di Bari, Romolo Nonno, Franco Cardone, Marco Sbriccoli, Silvia Graziano, Loredana Ingrosso, Michele Fiorini, Angelina Valanzano, Giulia Pasini, Anna Poleggi, Ramona Vinci, Anna Ladogana, Maria Puopolo, Salvatore Monaco, Umberto Agrimi, Gianluigi Zanusso, Maurizio Pocchiari
In 2007, we reported a patient with an atypical form of Creutzfeldt-Jakob disease (CJD), heterozygous for methionine-valine (MV) at codon 129, who showed a novel pathological prion protein (PrP(TSE)) conformation with an atypical glycoform (AG) profile and an intraneuronal PrP deposition. In the present study, we further characterized the conformational properties of this pathological prion protein (PrP(TSE) MV(AG)) showing that PrP(TSE) MV(AG) is composed by multiple conformers with biochemical properties distinct from PrP(TSE) type 1 and type 2 of MV sporadic CJD (sCJD)...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28283281/trends-in-vitreoretinal-procedures-for-medicare-beneficiaries-2000-to-2014
#13
Michael D McLaughlin, John C Hwang
TOPIC: The purpose of this study was to identify changes in use for vitreoretinal procedures by measuring the number of allowed services using data from the US Medicare Part B Fee-for-Service (FFS) beneficiaries and their providers. CLINICAL RELEVANCE: To analyze vitreoretinal procedural trends, which may indicate standard of care and importance of developing methods of treatments. METHODS: Medicare Part B National Summary Data Files for calendar years 2000 to 2014 were used to identify the number of allowed services for vitreoretinal procedures and commonly used pharmacologic agents...
May 2017: Ophthalmology
https://www.readbyqxmd.com/read/28282030/platelet-rich-plasma-for-regeneration-of-neural-feedback-pathways-around-dental-implants-a-concise-review-and-outlook-on-future-possibilities
#14
REVIEW
Yan Huang, Michael M Bornstein, Ivo Lambrichts, Hai-Yang Yu, Constantinus Politis, Reinhilde Jacobs
Along with the development of new materials, advanced medical imaging and surgical techniques, osseointegrated dental implants are considered a successful and constantly evolving treatment modality for the replacement of missing teeth in patients with complete or partial edentulism. The importance of restoring the peripheral neural feedback pathway and thus repairing the lack of periodontal mechanoreceptors after tooth extraction has been highlighted in the literature. Nevertheless, regenerating the nerve fibers and reconstructing the neural feedback pathways around osseointegrated implants remain a challenge...
March 2017: International Journal of Oral Science
https://www.readbyqxmd.com/read/28265109/comparative-evaluation-of-leukocyte-and-platelet-rich-plasma-and-pure-platelet-rich-plasma-for-cartilage-regeneration
#15
Zhengliang Xu, Wenjing Yin, Yuelei Zhang, Xin Qi, Yixuan Chen, Xuetao Xie, Changqing Zhang
Platelet-rich plasma (PRP) has gained growing popularity in the treatment of articular cartilage lesions in the last decade. However, the potential harmful effects of leukocytes in PRP on cartilage regeneration have seldom been studied in vitro, and not at all in vivo yet. The objective of the present study is to compare the effects of leukocyte- and platelet-rich plasma (L-PRP) and pure platelet-rich plasma (P-PRP) on cartilage repair and NF-κB pathway, in order to explore the mechanism underlying the function of leukocytes in PRP in cartilage regeneration...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28255815/effects-of-prion-protein-devoid-of-the-n-terminal-residues-25-50-on-prion-pathogenesis-in-mice
#16
Nandita Rani Das, Hironori Miyata, Hideyuki Hara, Keiji Uchiyama, Junji Chida, Masashi Yano, Hitomi Watanabe, Gen Kondoh, Suehiro Sakaguchi
The N-terminal polybasic region of the normal prion protein, PrP(C), which encompasses residues 23-31, is important for prion pathogenesis by affecting conversion of PrP(C) into the pathogenic isoform, PrP(Sc). We previously reported transgenic mice expressing PrP with residues 25-50 deleted in the PrP-null background, designated as Tg(PrP∆preOR)/Prnp (0/0) mice. Here, we produced two new lines of Tg(PrP∆preOR)/Prnp (0/0) mice, each expressing the mutant protein, PrP∆preOR, 1.1 and 1.6 times more than PrP(C) in wild-type mice, and subsequently intracerebrally inoculated RML and 22L prions into them...
March 2, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28250130/pathways-of-prion-spread-during-early-chronic-wasting-disease-in-deer
#17
Clare E Hoover, Kristen A Davenport, Davin M Henderson, Nathaniel D Denkers, Candace K Mathiason, Claudio Soto, Mark D Zabel, Edward A Hoover
Among prion infections, two scenarios of prion spread are generally observed: (a) early lymphoid tissue replication or (b) direct neuroinvasion without substantial antecedent lymphoid amplification. In nature, cervids are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation. However, knowledge of chronological events in prion spread during early infection remains incomplete...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28245395/-preparation-of-platelet-rich-plasma-from-the-white-slurry-and-its-effect-on-msc-proliferation
#18
Ke-Tao Wang, Zhong-Li Li, Heng Zhu, Yuan-Yuan Qin, Yi-Meng Yang, Ji Li, Ru-Ju Lv, Yuan-Lin Liu, Ning Mao, Yi Zhang
OBJECTIVE: To isolate platelet-rich plasma(PRP) from the white slurry(WS), a depleted fraction of the clinical blood supply, so as to provide an easier method to harvest PRP for related studies and clinical use. METHODS: The protocols preparing PRP from whole blood and WS were compared. The morphological characteristics of the different PRPs were observed under transmission electron microscope; the expression of the platelet markers CD41a and CD42b were detected by the flow cytometry...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28210651/analysis-of-platelet-rich-plasma-extraction-variations-in-platelet-and-blood-components-between-4-common-commercial-kits
#19
Jane Fitzpatrick, Max K Bulsara, Paul Robert McCrory, Martin D Richardson, Ming Hao Zheng
BACKGROUND: Platelet-rich plasma (PRP) has been extensively used as a treatment in tissue healing in tendinopathy, muscle injury, and osteoarthritis. However, there is variation in methods of extraction, and this produces different types of PRP. PURPOSE: To determine the composition of PRP obtained from 4 commercial separation kits, which would allow assessment of current classification systems used in cross-study comparisons. STUDY DESIGN: Controlled laboratory study...
January 2017: Orthopaedic Journal of Sports Medicine
https://www.readbyqxmd.com/read/28202758/endogenous-brain-lipids-inhibit-prion-amyloid-formation-in-vitro
#20
Clare E Hoover, Kristen A Davenport, Davin M Henderson, Mark D Zabel, Edward A Hoover
The normal cellular prion protein (PrP(C)) resides in detergent-resistant outer membrane lipid rafts in which conversion to the pathogenic misfolded form is believed to occur. Once misfolding occurs, the pathogenic isoform polymerizes into highly stable amyloid fibrils. In vitro assays have demonstrated an intimate association between prion conversion and lipids, specifically phosphatidylethanolamine, which is a critical cofactor in the formation of synthetic infectious prions. In the current work, we demonstrate an alternative inhibitory function of lipids in the prion conversion process as assessed in vitro by real-time, quaking induced conversion (RT-QuIC)...
February 15, 2017: Journal of Virology
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