IF 2.3 3区生物学

Prion Pub Date : 2018-03-04 Epub Date: 2018-03-09 DOI: 10.1080/19336896.2018.1436926

Natsumi Saito, Tomohiko Ishihara, Kensaku Kasuga, Mana Nishida, Takanobu Ishiguro, Hiroaki Nozaki, Takayoshi Shimohata, Osamu Onodera, Masatoyo Nishizawa

引用次数: 1

A Chinese patient of P102L Gerstmann-Sträussler-Scheinker disease contains three other disease-associated mutations in SYNE1. 一名P102L Gerstmann-Sträussler-Scheinker疾病的中国患者在SYNE1中含有三个其他疾病相关突变。

IF 2.3 3区生物学

Prion Pub Date : 2018-03-04 Epub Date: 2018-04-02 DOI: 10.1080/19336896.2018.1447733

Jing Wang, Kang Xiao, Wei Zhou, Chen Gao, Cao Chen, Qi Shi, Xiao-Ping Dong

{"title":"A Chinese patient of P102L Gerstmann-Sträussler-Scheinker disease contains three other disease-associated mutations in SYNE1.","authors":"Jing Wang, Kang Xiao, Wei Zhou, Chen Gao, Cao Chen, Qi Shi, Xiao-Ping Dong","doi":"10.1080/19336896.2018.1447733","DOIUrl":"https://doi.org/10.1080/19336896.2018.1447733","url":null,"abstract":"Gerstmann-Sträussler-Scheinker disease (GSS) with the P102L mutation in PRNP gene is characterized with progressive cerebellar dysfunction clinically and PrPSc plaques neurologically. Due to the cerebellar ataxia in the early stage, GSS P102L is often misdiagnosed as other neurodegenerative disorders. We presented here a 49-year-old female patient with proven P102L PRNP mutation, and three heterologous mutations in hereditary ataxias associated gene SYNE1, including p.V3643L, p.M3376V and p.T2860A. The patient appeared progressive unsteady gait in early stage and developed the Creutzfeldt-Jacob disease (CJD) - associated clinical manifestations, including progressive dementia, myoclonus, pyramidal and extrapyramidal signs. She is still alive but with akinetic mutism 21 months after onset. Observation of intense signal changes in cortical regions (cortical ribboning) in diffusion weighted imaging (DWI) MRI scanning and positive protein 14-3-3 in cerebrospinal fluid (CSF) proposed the diagnosis of sporadic CJD. The final diagnosis of P102L GSS was made after PRNP sequencing.","PeriodicalId":54585,"journal":{"name":"Prion","volume":"12 2","pages":"150-155"},"PeriodicalIF":2.3,"publicationDate":"2018-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2018.1447733","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35887182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Neuronal pathophysiology featuring PrP^C and its control over Ca²⁺ metabolism. 以PrPC为特征的神经元病理生理及其对Ca2+代谢的控制。

IF 2.3 3区生物学

Prion Pub Date : 2018-01-02 Epub Date: 2018-01-05 DOI: 10.1080/19336896.2017.1412912

Alessandro Bertoli, M Catia Sorgato

{"title":"Neuronal pathophysiology featuring PrPC and its control over Ca2+ metabolism.","authors":"Alessandro Bertoli, M Catia Sorgato","doi":"10.1080/19336896.2017.1412912","DOIUrl":"https://doi.org/10.1080/19336896.2017.1412912","url":null,"abstract":"Calcium (Ca2+) is an intracellular second messenger that ubiquitously masters remarkably diverse biological processes, including cell death. Growing evidence substantiates an involvement of the prion protein (PrPC) in regulating neuronal Ca2+ homeostasis, which could rationalize most of the wide range of functions ascribed to the protein. We have recently demonstrated that PrPC controls extracellular Ca2+ fluxes, and mitochondrial Ca2+ uptake, in neurons stimulated with glutamate (De Mario et al., J Cell Sci 2017; 130:2736-46), suggesting that PrPC protects neurons from threatening Ca2+ overloads and excitotoxicity. In light of these results and of recent reports in the literature, here we review the connection of PrPC with Ca2+ metabolism and also provide some speculative hints on the physiologic outcomes of this link. In addition, because PrPC is implicated in neurodegenerative diseases, including prion disorders and Alzheimer's disease, we will also discuss possible ways by which disruption of PrPC-Ca2+ association could be mechanistically connected with these pathologies.","PeriodicalId":54585,"journal":{"name":"Prion","volume":"12 1","pages":"28-33"},"PeriodicalIF":2.3,"publicationDate":"2018-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2017.1412912","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35635641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Overexpression of a conserved HSP40 chaperone reduces toxicity of several neurodegenerative disease proteins. 保守的HSP40伴侣蛋白过表达可降低几种神经退行性疾病蛋白的毒性。

IF 2.3 3区生物学

Prion Pub Date : 2018-01-02 Epub Date: 2018-01-31 DOI: 10.1080/19336896.2017.1423185

Sei-Kyoung Park, Fatih Arslan, Vydehi Kanneganti, Sami J Barmada, Pravinkumar Purushothaman, Subhash Chandra Verma, Susan W Liebman

{"title":"Overexpression of a conserved HSP40 chaperone reduces toxicity of several neurodegenerative disease proteins.","authors":"Sei-Kyoung Park, Fatih Arslan, Vydehi Kanneganti, Sami J Barmada, Pravinkumar Purushothaman, Subhash Chandra Verma, Susan W Liebman","doi":"10.1080/19336896.2017.1423185","DOIUrl":"https://doi.org/10.1080/19336896.2017.1423185","url":null,"abstract":"TDP-43 and FUS are DNA/RNA binding proteins associated with neuronal inclusions in amyotrophic lateral sclerosis (ALS) patients. Other neurodegenerative diseases are also characterized by neuronal protein aggregates, e.g. Huntington's disease, associated with polyglutamine (polyQ) expansions in the protein huntingtin. Here we discuss our recent paper establishing similarities between aggregates of TDP-43 that have short glutamine and asparagine (Q/N)-rich modules and are soluble in detergents, with those of polyQ and PIN4C that have large Q/N-rich domains and are detergent-insoluble. We also present new, similar data for FUS. Together, we show that like overexpression of polyQ or PIN4C, overexpression of FUS or TDP-43 causes inhibition of the ubiquitin proteasome system (UPS) and toxicity, both of which are mitigated by overexpression of the Hsp40 chaperone Sis1. Also, in all cases toxicity is enhanced by the [PIN+] prion. In addition, we show that the Sis1 mammalian homolog DNAJBI reduces toxicity arising from overexpressed FUS and TDP-43 respectively in human embryonic kidney cells and primary rodent neurons. The common properties of these proteins suggest that heterologous aggregates may enhance the toxicity of a variety of disease-related aggregating proteins, and further that chaperones and the UPS may be key therapeutic targets for diseases characterized by protein inclusions.","PeriodicalId":54585,"journal":{"name":"Prion","volume":"12 1","pages":"16-22"},"PeriodicalIF":2.3,"publicationDate":"2018-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2017.1423185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35715639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 23

Pathological progression of genetic Creutzfeldt-Jakob disease with a PrP V180I mutation. 伴有PrP V180I突变的遗传性克雅氏病的病理进展

IF 2.3 3区生物学

Prion Pub Date : 2018-01-02 Epub Date: 2018-01-31 DOI: 10.1080/19336896.2017.1414130

Akio Akagi, Yasushi Iwasaki, Maya Mimuro, Tetsuyuki Kitamoto, Masahito Yamada, Mari Yoshida

{"title":"Pathological progression of genetic Creutzfeldt-Jakob disease with a PrP V180I mutation.","authors":"Akio Akagi, Yasushi Iwasaki, Maya Mimuro, Tetsuyuki Kitamoto, Masahito Yamada, Mari Yoshida","doi":"10.1080/19336896.2017.1414130","DOIUrl":"https://doi.org/10.1080/19336896.2017.1414130","url":null,"abstract":"In comparison to sporadic Creutzfeldt-Jakob disease (sCJD) with MM1-type and MM2- cortical (MM2C)-type, genetic CJD with a prion protein gene V180I mutation (V180I gCJD) is clinically characterized by onset at an older age, slower progress, and the absence of visual disturbances or cerebellar symptoms. In terms of pathological characteristics, gliosis and neuronal loss are generally milder in degree, and characteristic spongiform change can be observed at both the early and advanced stages. However, little is known on the progress of spongiform change over time or its mechanisms. In this study, to elucidate the pathological course of V180I gCJD, statistical analysis of the size and dispersion of the major diameters of vacuoles in six V180I gCJD cases was performed, with five MM1-type sCJD and MM2C-type sCJD cases as controls. As a result, V180I gCJD showed no significant difference in vacuolar diameter regardless of disease duration. In addition, the dispersion of the major diameters of vacuoles in V180I gCJD was larger than that in the MM1-type, which was smaller than that in the MM2C-type. We speculated that the absence of difference in the size of the vacuoles regardless of disease duration suggests that tissue rarefaction does not result from the expansion of vacuole size and increase in number of vacuoles in V180Ig CJD. These features were considered to be significant pathological findings of V180I gCJD.","PeriodicalId":54585,"journal":{"name":"Prion","volume":"12 1","pages":"54-62"},"PeriodicalIF":2.3,"publicationDate":"2018-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2017.1414130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35677128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14

Genetic effects of PRNP gene insertion/deletion (indel) on phenotypic traits in sheep. PRNP基因插入/缺失对绵羊表型性状的遗传影响。

IF 2.3 3区生物学

Prion Pub Date : 2018-01-02 Epub Date: 2018-02-02 DOI: 10.1080/19336896.2017.1405886

Jie Li, Sarantsetseg Erdenee, Shaoli Zhang, Zhenyu Wei, Meng Zhang, Yunyun Jin, Hui Wu, Hong Chen, Xiuzhu Sun, Hongwei Xu, Yong Cai, Xianyong Lan

{"title":"Genetic effects of PRNP gene insertion/deletion (indel) on phenotypic traits in sheep.","authors":"Jie Li, Sarantsetseg Erdenee, Shaoli Zhang, Zhenyu Wei, Meng Zhang, Yunyun Jin, Hui Wu, Hong Chen, Xiuzhu Sun, Hongwei Xu, Yong Cai, Xianyong Lan","doi":"10.1080/19336896.2017.1405886","DOIUrl":"https://doi.org/10.1080/19336896.2017.1405886","url":null,"abstract":"Prion protein (PRNP) gene is well known for affecting mammal transmissible spongiform encephalopathies (TSE), and is also reported to regulate phenotypic traits (e.g. growth traits) in healthy ruminants. To identify the insertion/deletion (indel) variations of the PRNP gene and evaluate their effects on growth traits, 768 healthy individuals from five sheep breeds located in China and Mongolia were identified and analyzed. Herein, four novel indel polymorphisms, namely, Intron-1-insertion-7bp (I1-7bp), Intron-2-insertion-15bp (I2-15bp), Intron-2-insertion-19bp (I2-19bp), and 3' UTR-insertion-7bp (3' UTR-7bp), were found in the sheep PRNP gene. In five analyzed breeds, the minor allelic frequencies (MAF) of the above indels were in the range of 0.008 to 0.986 (I1-7bp), 0.113 to 0.336 (I2-15bp), 0.281 to 0.510 (I2-19bp), and 0.040 to 0.238 (3' UTR-7bp). Additionally, there were 15 haplotypes and the haplotype 'II2-15bp-D3'UTR-7bp-DI2-19bp-DI1-7bp' had the highest frequency, which varied from 0.464 to 0.629 in five breeds. Moreover, association analysis revealed that all novel indel polymorphisms were significantly associated with 13 different growth traits (P < 0.05). Particularly, the influences of I2-15bp on chest width (P = 0.001) in Small Tail Han sheep (ewe), 3' UTR-7bp on chest circumference (P = 0.003) in Hu sheep, and I2-19bp on tail length (P = 0.001) in Tong sheep, were highly significant (P < 0.01). These findings may be a further step toward the detection of indel-based typing within and across sheep breeds, and of promising target loci for accelerating the progress of marker-assisted selection in sheep breeding.","PeriodicalId":54585,"journal":{"name":"Prion","volume":"12 1","pages":"42-53"},"PeriodicalIF":2.3,"publicationDate":"2018-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2017.1405886","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35788154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 37

Somatostatin in Alzheimer's disease: A new Role for an Old Player. 生长抑素在阿尔茨海默病中的新作用。

IF 2.3 3区生物学

Prion Pub Date : 2018-01-02 Epub Date: 2018-01-31 DOI: 10.1080/19336896.2017.1405207

Michael Solarski, Hansen Wang, Holger Wille, Gerold Schmitt-Ulms

{"title":"Somatostatin in Alzheimer's disease: A new Role for an Old Player.","authors":"Michael Solarski, Hansen Wang, Holger Wille, Gerold Schmitt-Ulms","doi":"10.1080/19336896.2017.1405207","DOIUrl":"https://doi.org/10.1080/19336896.2017.1405207","url":null,"abstract":"The amyloid beta (Aβ) peptide is central to the pathogenesis of Alzheimer's disease (AD). Insights into Aβ-interacting proteins are critical for understanding the molecular mechanisms underlying Aβ-mediated toxicity. We recently undertook an in-depth in vitro interrogation of the Aβ1-42 interactome using human frontal lobes as the biological source material and taking advantage of advances in mass spectrometry performance characteristics. These analyses uncovered the small cyclic neuropeptide somatostatin (SST) to be the most selectively enriched binder to oligomeric Aβ1-42. Subsequent validation experiments revealed that SST interferes with Aβ fibrillization and promotes the formation of Aβ assemblies characterized by a 50-60 kDa SDS-resistant core. The distributions of SST and Aβ overlap in the brain and SST has been linked to AD by several additional observations. This perspective summarizes this body of literature and draws attention to the fact that SST is one of several neuropeptide hormones that acquire amyloid properties before their synaptic release. The latter places the interaction between SST and Aβ among an increasing number of observations that attest to the ability of amyloidogenic proteins to influence each other. A model is presented which attempts to reconcile existing data on the involvement of SST in the AD etiology.","PeriodicalId":54585,"journal":{"name":"Prion","volume":"12 1","pages":"1-8"},"PeriodicalIF":2.3,"publicationDate":"2018-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2017.1405207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35605277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 39

The role of the prion protein in the internalization of α-synuclein amyloids. 朊蛋白在α-突触核蛋白淀粉样蛋白内化中的作用。

IF 2.3 3区生物学

Prion Pub Date : 2018-01-02 Epub Date: 2018-01-31 DOI: 10.1080/19336896.2017.1423186

Elena De Cecco, Giuseppe Legname

{"title":"The role of the prion protein in the internalization of α-synuclein amyloids.","authors":"Elena De Cecco, Giuseppe Legname","doi":"10.1080/19336896.2017.1423186","DOIUrl":"https://doi.org/10.1080/19336896.2017.1423186","url":null,"abstract":"Synucleinopathies are a group of neurodegenerative diseases characterized by the accumulation of α-synuclein amyloids in several regions of the brain. α-Synuclein fibrils are able to spread via cell-to-cell transfer, and once inside the cells, they can template the misfolding and aggregation of the endogenous α-synuclein. Multiple mechanisms have been shown to participate in the process of propagation: endocytosis, tunneling nanotubes and macropinocytosis. Recently, we published a research showing that the cellular form of the prion protein (PrPC) acts as a receptor for α-synuclein amyloid fibrils, facilitating their internalization through and endocytic pathway. This interaction occurs by a direct interaction between the fibrils and the N-terminal domain of PrPC. In cell lines expressing the pathological form of PrP (PrPSc), the binding between PrPC and α-synuclein fibrils prevents the formation and accumulation of PrPSc, since PrPC is no longer available as a substrate for the pathological conversion templated by PrPSc. On the contrary, PrPSc deposits are cleared over passages, probably due to the increased processing of PrPC into the neuroprotective fragments N1 and C1. Starting from these data, in this work we present new insights into the role of PrPC in the internalization of protein amyloids and the possible therapeutic applications of these findings.","PeriodicalId":54585,"journal":{"name":"Prion","volume":"12 1","pages":"23-27"},"PeriodicalIF":2.3,"publicationDate":"2018-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2017.1423186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35714865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 27

The associations of two SNPs in miRNA-146a and one SNP in ZBTB38-RASA2 with the disease susceptibility and the clinical features of the Chinese patients of sCJD and FFI. miRNA-146a中2个SNP和ZBTB38-RASA2中1个SNP与中国sCJD和FFI患者疾病易感性和临床特征的关系

IF 2.3 3区生物学

Prion Pub Date : 2018-01-02 DOI: 10.1080/19336896.2017.1405885

Chen Gao, Qiang Shi, Jing Wei, Wei Zhou, Kang Xiao, Jing Wang, Qi Shi, Xiao-Ping Dong

{"title":"The associations of two SNPs in miRNA-146a and one SNP in ZBTB38-RASA2 with the disease susceptibility and the clinical features of the Chinese patients of sCJD and FFI.","authors":"Chen Gao, Qiang Shi, Jing Wei, Wei Zhou, Kang Xiao, Jing Wang, Qi Shi, Xiao-Ping Dong","doi":"10.1080/19336896.2017.1405885","DOIUrl":"https://doi.org/10.1080/19336896.2017.1405885","url":null,"abstract":"Prion diseases are a group of fatal neurodegenerative disorders that affect humans and animals. Besides of the pathological agent, prion, there are some elements that can influence or determine susceptibility to prion infection and the clinical phenotype of the diseases, e.g., the polymorphism in PRNP gene. Another polymorphism in ZBTB38-RASA2 has been observed to be associated with the susceptibility of sporadic Creutzfeldt-Jacob disease (sCJD) in UK. MicroRNAs are endogenous small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. In this study, two polymorphic loci in miR-146a (rs2910164 and rs57095329) and one locus in ZBTB38-RASA2 (rs295301) of 561 Chinese patients of sCJD and 31 cases of fatal familial insomnia (FFI) were screened by PCR and sequencing. Our data did not figure out any association of those three SNPs with the susceptibility of sCJD. However, a significant association of the SNP of rs57095329 in miR-146a showed the association with the susceptibility of FFI. Additionally, the SNP of rs57095329 showed statistical significances with the appearances of mutism and the positive of cerebrospinal fluid (CSF) protein 14-3-3 in sCJD patients, while the SNP of ZBTB38-RASA2 was significantly related with the appearance of myoclonus in sCJD patients. It indicates that the SNPs of ZBTB38-RASA2 and miR-146a are not associated with the susceptibility of the Chinese sCJD patients, but may influence the appearances of clinical manifestations somehow.","PeriodicalId":54585,"journal":{"name":"Prion","volume":"12 1","pages":"34-41"},"PeriodicalIF":2.3,"publicationDate":"2018-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2017.1405885","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35321617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Differential effects of divalent cations on elk prion protein fibril formation and stability. 二价阳离子对麋鹿朊蛋白原纤维形成及稳定性的差异影响。

IF 2.3 3区生物学

Prion Pub Date : 2018-01-02 Epub Date: 2018-01-31 DOI: 10.1080/19336896.2017.1423187

Daniel Samorodnitsky, Eric M Nicholson

{"title":"Differential effects of divalent cations on elk prion protein fibril formation and stability.","authors":"Daniel Samorodnitsky, Eric M Nicholson","doi":"10.1080/19336896.2017.1423187","DOIUrl":"https://doi.org/10.1080/19336896.2017.1423187","url":null,"abstract":"Misfolding of the normally folded prion protein of mammals (PrPC) into infectious fibrils causes a variety of diseases, from scrapie in sheep to chronic wasting disease (CWD) in cervids. The misfolded form of PrPC, termed PrPSc, or in this case PrPCWD, interacts with PrPC to create more PrPCWD. This process is not clearly defined but is affected by the presence and interactions of biotic and abiotic cofactors. These include nucleic acids, lipids, glycosylation, pH, and ionic character. PrPC has been shown to act as a copper-binding protein in vivo, though it also binds to other divalents as well. The significance of this action has not been conclusively elucidated. Previous reports have shown that metal binding sites occur throughout the N-terminal region of PrPC. Other cations like manganese have also been shown to affect PrPC abundance in a transcript-independent fashion. Here, we examined the ability of different divalent cations to influence the stability and in vitro conversion of two variants of PrP from elk (L/M132, 26-234). We find that copper and zinc de-stabilize PrP. We also find that PrP M132 exhibits a greater degree of divalent cation induced destabilization than L132. This supports findings that leucine at position 132 confers resistance to CWD, while M132 is susceptible. However, in vitro conversion of PrP is equally suppressed by either copper or zinc, in both L132 and M132 backgrounds. This report demonstrates the complex importance of ionic character on the PrPC folding pathway selection on the route to PrPSc formation.","PeriodicalId":54585,"journal":{"name":"Prion","volume":"12 1","pages":"63-71"},"PeriodicalIF":2.3,"publicationDate":"2018-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2017.1423187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35717124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Prion最新文献