IF 2.3 3区生物学

Prion Pub Date : 2021-12-01 DOI: 10.1080/19336896.2021.1964326

Utpal Kumar Adhikari, Mourad Tayebi

{"title":"Epitope-specific anti-PrP antibody toxicity: a comparative in-silico study of human and mouse prion proteins.","authors":"Utpal Kumar Adhikari, Mourad Tayebi","doi":"10.1080/19336896.2021.1964326","DOIUrl":"https://doi.org/10.1080/19336896.2021.1964326","url":null,"abstract":"Despite having therapeutic potential, anti-PrP antibodies caused a major controversy due to their neurotoxic effects. For instance, treating mice with ICSM antibodies delayed prion disease onset, but both were found to be either toxic or innocuous to neurons by researchers following cross-linking PrPC. In order to elucidate and understand the reasons that led to these contradictory outcomes, we conducted a comprehensive in silico study to assess the antibody-specific toxicity. Since most therapeutic anti-PrP antibodies were generated against human truncated recombinant PrP91-231 or full-length mouse PrP23-231, we reasoned that host specificity (human vs murine) of PrPC might influence the nature of the specific epitopes recognized by these antibodies at the structural level possibly explaining the 'toxicity' discrepancies reported previously. Initially, molecular dynamics simulation and pro-motif analysis of full-length human (hu)PrP and mouse (mo)PrP 3D structure displayed conspicuous structural differences between huPrP and moPrP. We identified 10 huPrP and 6 moPrP linear B-cell epitopes from the prion protein 3D structure where 5 out of 10 huPrP and 3 out of 6 moPrP B-cell epitopes were predicted to be potentially toxic in immunoinformatics approaches. Herein, we demonstrate that some of the predicted potentially 'toxic' epitopes identified by the in silico analysis were similar to the epitopes recognized by the toxic antibodies such as ICSM18 (146-159), POM1 (138-147), D18 (133-157), ICSM35 (91-110), D13 (95-103) and POM3 (95-100). This in silico study reveals the role of host specificity of PrPC in epitope-specific anti-PrP antibody toxicity.","PeriodicalId":54585,"journal":{"name":"Prion","volume":"15 1","pages":"155-176"},"PeriodicalIF":2.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/10/99/KPRN_15_1964326.PMC8900626.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39504517","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: 0

Monomeric a-synuclein (aS) inhibits amyloidogenesis of human prion protein (hPrP) by forming a stable aS-hPrP hetero-dimer. 单体a-synuclein (aS)通过形成稳定的aS-hPrP异二聚体抑制人朊蛋白(hPrP)淀粉样蛋白的形成。

IF 2.3 3区生物学

Prion Pub Date : 2021-12-01 DOI: 10.1080/19336896.2021.1910176

Satoshi Yamashita, Yuji O Kamatari, Ryo Honda, Ayumi Niwa, Hiroyuki Tomiata, Akira Hara, Kazuo Kuwata

{"title":"Monomeric a-synuclein (aS) inhibits amyloidogenesis of human prion protein (hPrP) by forming a stable aS-hPrP hetero-dimer.","authors":"Satoshi Yamashita, Yuji O Kamatari, Ryo Honda, Ayumi Niwa, Hiroyuki Tomiata, Akira Hara, Kazuo Kuwata","doi":"10.1080/19336896.2021.1910176","DOIUrl":"https://doi.org/10.1080/19336896.2021.1910176","url":null,"abstract":"Intermolecular interaction between hPrP and αS was investigated using high-speed atomic force microscopy, dynamic light scattering, and nuclear magnetic resonance. We found that hPrP spontaneously gathered and naturally formed oligomers. Upon addition of monomer αS with a disordered conformation, poly-dispersive property of hPrP was lost, and hetero-dimer formation started quite coherently, and further oligomerization was not observed. Solution structure of hPrP-αS dimer was firstly characterized using hetero-nuclear NMR spectroscopy. In this hetero-dimeric complex, C-terminal helical region of hPrP was in the molten-globule like state, while specific sites including hot spot and C-terminal region of αS selectively interacted with hPrP. Thus αS may suppress amyloidogenesis of hPrP by trapping the hPrP intermediate by the formation of a stable hetero-dimer with hPrP.Abbreviations: hPrP, human prion protein of amino acid residues of 23-231; PrPC, cellular form of prion protein; PrPSc, scrapie form of prion protein, HS-AFM; high speed atomic force microscopy; αS, α-synuclein; DLS, dynamic light scattering.","PeriodicalId":54585,"journal":{"name":"Prion","volume":"15 1","pages":"37-43"},"PeriodicalIF":2.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2021.1910176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25585874","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: 2

Prion domains as a driving force for the assembly of functional nanomaterials. 朊病毒结构域作为功能纳米材料组装的驱动力。

IF 2.3 3区生物学

Prion Pub Date : 2020-12-01 DOI: 10.1080/19336896.2020.1785659

Weiqiang Wang, Salvador Ventura

{"title":"Prion domains as a driving force for the assembly of functional nanomaterials.","authors":"Weiqiang Wang, Salvador Ventura","doi":"10.1080/19336896.2020.1785659","DOIUrl":"https://doi.org/10.1080/19336896.2020.1785659","url":null,"abstract":"ABSTRACT Amyloids display a highly ordered fibrillar structure. Many of these assemblies appear associated with human disease. However, the controllable, stable, tunable, and robust nature of amyloid fibrils can be exploited to build up remarkable nanomaterials with a wide range of applications in biomedicine and biotechnology. Functional prions constitute a particular class of amyloids. These transmissible proteins exhibit a modular architecture, with a disordered prion domain responsible for the assembly and one or more globular domains that account for the activity. Importantly, the original globular protein can be replaced with any protein of interest, without compromising the fibrillation potential. These genetic fusions form fibrils in which the globular domain remains folded, rendering functional nanostructures. However, in some cases, steric hindrance restricts the activity of these fibrils. This limitation can be solved by dissecting prion domains into shorter sequences that keep their self-assembling properties while allowing better access to the active protein in the fibrillar state. In this review, we will discuss the properties of prion-like functional nanomaterials and the amazing applications of these biocompatible fibrillar arrangements.","PeriodicalId":54585,"journal":{"name":"Prion","volume":"14 1","pages":"170-179"},"PeriodicalIF":2.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2020.1785659","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10637767","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

Experimental oral transmission of chronic wasting disease to sika deer (Cervus nippon). 梅花鹿慢性消耗性疾病的实验性口腔传播。

IF 2.3 3区生物学

Prion Pub Date : 2020-12-01 DOI: 10.1080/19336896.2020.1857038

Hyun-Joo Sohn, Gordon Mitchell, Yoon Hee Lee, Hyo Jin Kim, Kyung-Je Park, Antanas Staskevicus, Ines Walther, Andrei Soutyrine, Aru Balachandran

{"title":"Experimental oral transmission of chronic wasting disease to sika deer (Cervus nippon).","authors":"Hyun-Joo Sohn, Gordon Mitchell, Yoon Hee Lee, Hyo Jin Kim, Kyung-Je Park, Antanas Staskevicus, Ines Walther, Andrei Soutyrine, Aru Balachandran","doi":"10.1080/19336896.2020.1857038","DOIUrl":"https://doi.org/10.1080/19336896.2020.1857038","url":null,"abstract":"Chronic wasting disease (CWD) affects a broad array of cervid species and continues to be detected in an expanding geographic range. Initially introduced into the Republic of Korea through the importation of CWD-infected elk (Cervus canadensis), additional cases of CWD were subsequently detected in farmed Korean elk and sika deer (Cervus nippon). Wild and farmed sika deer are found in many regions of Asia, North America, and Europe, although natural transmission to this species has not been detected outside of the Republic of Korea. In this study, the oral transmission of CWD to sika deer was investigated using material from CWD-affected elk. Pathological prion (PrPCWD) immunoreactivity was detected in oropharyngeal lymphoid tissues of one sika deer at 3.9 months post-inoculation (mpi) and was more widely distributed in a second sika deer examined at 10.9 mpi. The remaining four sika deer progressed to clinical disease between 21 and 24 mpi. Analysis of PrPCWD tissue distribution in clinical sika deer revealed widespread deposition in central and peripheral nervous systems, lymphoreticular tissues, and the gastrointestinal tract. Prion protein gene (PRNP) sequences of these sika deer were identical and consistent with those reported in natural sika deer populations. These findings demonstrate the efficient oral transmission of CWD from elk to sika deer.","PeriodicalId":54585,"journal":{"name":"Prion","volume":" ","pages":"271-277"},"PeriodicalIF":2.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2020.1857038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38696443","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

The cellular prion protein promotes neuronal regeneration after acute nasotoxic injury. 细胞朊蛋白促进急性鼻毒性损伤后神经元再生。

IF 1.9 3区生物学

Prion Pub Date : 2020-12-01 DOI: 10.1080/19336896.2020.1714373

Lindsay E Parrie, Jenna A E Crowell, Julie A Moreno, Stephanie S Suinn, Glenn C Telling, Richard A Bessen

{"title":"The cellular prion protein promotes neuronal regeneration after acute nasotoxic injury.","authors":"Lindsay E Parrie, Jenna A E Crowell, Julie A Moreno, Stephanie S Suinn, Glenn C Telling, Richard A Bessen","doi":"10.1080/19336896.2020.1714373","DOIUrl":"10.1080/19336896.2020.1714373","url":null,"abstract":"Adult neurogenesis, analogous to early development, is comprised of several, often concomitant, processes including proliferation, differentiation, and formation of synaptic connections. However, due to continual, asynchronous turn-over, newly-born adult olfactory sensory neurons (OSNs) must integrate into existing circuitry. Additionally, OSNs express high levels of cellular prion protein (PrPC), particularly in the axon, which implies a role in this cell type. The cellular prion has been shown to be important for proper adult OSN neurogenesis primarily by stabilizing mature olfactory neurons within this circuitry. However, the role of PrPC on each specific adult neurogenic processes remains to be investigated in detail. To tease out the subtle effects of prion protein expression level, a large population of regenerating neurons must be investigated. The thyroid drug methimazole (MTZ) causes nearly complete OSN loss in rodents and is used as a model of acute olfactory injury, providing a mechanism to induce synchronized OSN regeneration. This study investigated the effect of PrPC on adult neurogenesis after acute nasotoxic injury. Altered PrPC levels affected olfactory sensory epithelial (OSE) regeneration, cell proliferation, and differentiation. Attempts to investigate the role of PrPC level on axon regeneration did not support previous studies, and glomerular targeting did not recover to vehicle-treated levels, even by 20 weeks. Together, these studies demonstrate that the cellular prion protein is critical for regeneration of neurons, whereby increased PrPC levels promote early neurogenesis, and that lack of PrPC delays the regeneration of this tissue after acute injury.","PeriodicalId":54585,"journal":{"name":"Prion","volume":"14 1","pages":"31-41"},"PeriodicalIF":1.9,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10764521","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: 0

Geographic variation in the PRNP gene and its promoter, and their relationship to chronic wasting disease in North American deer. 北美鹿PRNP基因及其启动子的地理变异及其与慢性消耗性疾病的关系

IF 2.3 3区生物学

Prion Pub Date : 2020-12-01 DOI: 10.1080/19336896.2020.1796250

Robert M Zink, Nadje Najar, Hernán Vázquez-Miranda, Brittaney L Buchanan, Duan Loy, Bruce W Brodersen

引用次数: 9

Age structuring and spatial heterogeneity in prion protein gene (PRNP) polymorphism in white-tailed deer. 白尾鹿朊病毒蛋白基因(PRNP)多态性的年龄结构及空间异质性

IF 2.3 3区生物学

Prion Pub Date : 2020-12-01 DOI: 10.1080/19336896.2020.1832947

Tyler K Chafin, Marlis R Douglas, Bradley T Martin, Zachery D Zbinden, Christopher R Middaugh, Jennifer R Ballard, M Cory Gray, Don White, Michael E Douglas

{"title":"Age structuring and spatial heterogeneity in prion protein gene (PRNP) polymorphism in white-tailed deer.","authors":"Tyler K Chafin, Marlis R Douglas, Bradley T Martin, Zachery D Zbinden, Christopher R Middaugh, Jennifer R Ballard, M Cory Gray, Don White, Michael E Douglas","doi":"10.1080/19336896.2020.1832947","DOIUrl":"https://doi.org/10.1080/19336896.2020.1832947","url":null,"abstract":"Chronic-wasting disease (CWD) is a prion-derived fatal neurodegenerative disease that has affected wild cervid populations on a global scale. Susceptibility has been linked unambiguously to several amino acid variants within the prion protein gene (PRNP). Quantifying their distribution across landscapes can provide critical information for agencies attempting to adaptively manage CWD. Here we attempt to further define management implications of PRNP polymorphism by quantifying the contemporary geographic distribution (i.e., phylogeography) of PRNP variants in hunter-harvested white-tailed deer (WTD; Odocoileus virginianus, N = 1433) distributed across Arkansas (USA), including a focal spot for CWD since detection of the disease in February 2016. Of these, PRNP variants associated with the well-characterized 96S non-synonymous substitution showed a significant increase in relative frequency among older CWD-positive cohorts. We interpreted this pattern as reflective of a longer life expectancy for 96S genotypes in a CWD-endemic region, suggesting either decreased probabilities of infection or reduced disease progression. Other variants showing statistical signatures of potential increased susceptibility, however, seemingly reflect an artefact of population structure. We also showed marked heterogeneity across the landscape in the prevalence of 'reduced susceptibility' genotypes. This may indicate, in turn, that differences in disease susceptibility among WTD in Arkansas are an innate, population-level characteristic that is detectable through phylogeographic analysis.","PeriodicalId":54585,"journal":{"name":"Prion","volume":" ","pages":"238-248"},"PeriodicalIF":2.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2020.1832947","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38512879","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

The role of cellular prion protein in lipid metabolism in the liver. 细胞朊蛋白在肝脏脂质代谢中的作用。

IF 2.3 3区生物学

Prion Pub Date : 2020-12-01 DOI: 10.1080/19336896.2020.1729074

Amandeep Singh Arora, Saima Zafar, Umair Latif, Franc Llorens, Mihm Sabine, Prateek Kumar, Waqas Tahir, Katrin Thüne, Mohsin Shafiq, Matthias Schmitz, Inga Zerr

{"title":"The role of cellular prion protein in lipid metabolism in the liver.","authors":"Amandeep Singh Arora, Saima Zafar, Umair Latif, Franc Llorens, Mihm Sabine, Prateek Kumar, Waqas Tahir, Katrin Thüne, Mohsin Shafiq, Matthias Schmitz, Inga Zerr","doi":"10.1080/19336896.2020.1729074","DOIUrl":"https://doi.org/10.1080/19336896.2020.1729074","url":null,"abstract":"Cellular prion protein (PrPC) is a plasma membrane glycophosphatidylinositol-anchored protein and it is involved in multiple functions, including neuroprotection and oxidative stress. So far, most of the PrPC functional research is done in neuronal tissue or cell lines; the role of PrPC in non-neuronal tissues such as liver is only poorly understood. To characterize the role of PrPC in the liver, a proteomics approach was applied in the liver tissue of PrPC knockout mice. The proteome analysis and biochemical validations showed an excessive fat accumulation in the liver of PrPC knockout mice with a change in mRNA expression of genes linked to lipid metabolism. In addition, the higher Bax to Bcl2 ratio, up-regulation of tgfb1 mRNA expression in PrPC knockout mice liver, further showed the evidences of metabolic disease. Over-expression of PrPC in fatty acid-treated AML12 hepatic cell line caused a reduction in excessive intracellular fat accumulation; shows association of PrPC levels and lipid metabolism. Therefore, based on observation of excessive fat globules in the liver of ageing PrPC knockout mice and the reduction of fat accumulation in AML12 cell line with PrPC over-expression, the role of PrPC in lipid metabolism is described.","PeriodicalId":54585,"journal":{"name":"Prion","volume":" ","pages":"95-108"},"PeriodicalIF":2.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2020.1729074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37708752","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: 3

Understanding Creutzfeldt-Jackob disease from a viewpoint of amyloidogenic evolvability. 从淀粉样变性进化的角度理解克雅氏病。

IF 2.3 3区生物学

Prion Pub Date : 2020-12-01 DOI: 10.1080/19336896.2020.1761514

Makoto Hashimoto, Gilbert Ho, Yoshiki Takamatsu, Ryoko Wada, Shuei Sugama, Masaaki Waragai, Eliezer Masliah, Takato Takenouchi

{"title":"Understanding Creutzfeldt-Jackob disease from a viewpoint of amyloidogenic evolvability.","authors":"Makoto Hashimoto, Gilbert Ho, Yoshiki Takamatsu, Ryoko Wada, Shuei Sugama, Masaaki Waragai, Eliezer Masliah, Takato Takenouchi","doi":"10.1080/19336896.2020.1761514","DOIUrl":"https://doi.org/10.1080/19336896.2020.1761514","url":null,"abstract":"Creutzfeldt-Jackob disease (CJD), the most common human prion disorder, is frequently accompanied by ageing-associated neurodegenerative conditions, such as Alzheimer's disease and Parkinson's disease. Although cross-seeding of amyloidogenic proteins (APs), including amyloid β and α-synuclein, may be critical in the co-morbidity of neurodegenerative disorders, the direct interaction of APs with prion protein (PrP), the central molecule involved in the pathogenesis of CJD, is unlikely. Currently, the nature of this biological interaction and its significance remain obscure. In this context, the objective of the present study is to discuss such interactions from the perspective of amyloidogenic evolvability, a putative function of APs. Hypothetically, both hereditary- and sporadic CJD might be attributed to the role of PrP in evolvability against multiple stressors, such as physical stresses relevant to concussions, which might be manifest through the antagonistic pleiotropy mechanism in ageing. Furthermore, accumulating evidence suggests that PrP- and other APs evolvability may negatively regulate each other. Provided that increased APs evolvability might be beneficial for acquired CJD in young adults, a dose-reduction of α-synuclein, a natural inhibitor of αS aggregation, might be therapeutically effective in upregulating APs evolvability. Collectively, a better understanding of amyloidogenic evolvability may lead to the development of novel therapies for CJD.","PeriodicalId":54585,"journal":{"name":"Prion","volume":" ","pages":"1-8"},"PeriodicalIF":2.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2020.1761514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37907238","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

Discovery of a multipotent chaperone, 1-(2,6-Difluorobenzylamino)-3-(1,2,3,4-tetrahydrocarbazol-9-yl)-propan-2-ol with the inhibitory effects on the proliferation of prion, cancer as well as influenza virus. 多能伴侣1-(2,6-二氟氨基苄)-3-(1,2,3,4-四氢咔唑-9-基)-丙二醇对朊病毒、癌症和流感病毒增殖的抑制作用的发现。

IF 2.3 3区生物学

Prion Pub Date : 2020-12-01 DOI: 10.1080/19336896.2020.1714372

Satoshi Yamashita, Ryo Honda, Mayuko Fukuoka, Tsutomu Kimura, Junji Hosokawa-Muto, Kazuo Kuwata

{"title":"Discovery of a multipotent chaperone, 1-(2,6-Difluorobenzylamino)-3-(1,2,3,4-tetrahydrocarbazol-9-yl)-propan-2-ol with the inhibitory effects on the proliferation of prion, cancer as well as influenza virus.","authors":"Satoshi Yamashita, Ryo Honda, Mayuko Fukuoka, Tsutomu Kimura, Junji Hosokawa-Muto, Kazuo Kuwata","doi":"10.1080/19336896.2020.1714372","DOIUrl":"https://doi.org/10.1080/19336896.2020.1714372","url":null,"abstract":"We previously discovered three carbazole derivatives, GJP14 (1-piperidinylmethyl-2-(1-oxo-6-methyl-1,2,3,4-tetrahydrocarbazol-9-yl)-ethan-1-ol) with anti-prion activity, GJC29 (benzylamino-3-(1,2,3,4-tetrahydrocarbazol-9-yl)-propan-2-ol) with anti-cancer activity, and THC19 (1-piperidinylmethyl-2-(1,2,3,4-tetrahydrocarnazol-9-yl)-ethan-1-ol) with anti-influenza virus activity. During optimization of GJP14 for the anti-prion activity, we discovered a compound, 1-(2,6-difluorobenzylamino)-3-(1,2,3,4-tetrahydrocarbazol-9-yl)-propan-2-ol, termed 5Y, had the most strong anti-prion activity among a series of newly synthesized derivatives. Intriguingly, we noticed that 5Y had also the most strong anti-colon cancer as well as the anti-influenza virus activities among derivatives. No significant toxicity of 5Y was observed. These results demonstrate that 5Y is a multipotent lead compound with unusually wide spectrum, and may be applicable to therapeutics targeting multiple diseases.Abbreviations: MoPrP: mouse prion protein of amino acid residues of 23-231; PrPC: cellular form of prion protein; PrPSc: scrapie form of prion protein.","PeriodicalId":54585,"journal":{"name":"Prion","volume":" ","pages":"42-46"},"PeriodicalIF":2.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336896.2020.1714372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37570806","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: 2

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