FEBS Journal最新文献_第8页

Inhibition of tau amyloid formation and disruption of its preformed fibrils by Naphthoquinone-Dopamine hybrid. 萘醌-多巴胺杂合物对tau淀粉样蛋白形成的抑制及其预形成原纤维的破坏。

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-07-01 Epub Date: 2021-02-18 DOI: 10.1111/febs.15741

Ashim Paul, Guru KrishnaKumar Viswanathan, Adi Huber, Elad Arad, Hamutal Engel, Raz Jelinek, Ehud Gazit, Daniel Segal

{"title":"Inhibition of tau amyloid formation and disruption of its preformed fibrils by Naphthoquinone-Dopamine hybrid.","authors":"Ashim Paul, Guru KrishnaKumar Viswanathan, Adi Huber, Elad Arad, Hamutal Engel, Raz Jelinek, Ehud Gazit, Daniel Segal","doi":"10.1111/febs.15741","DOIUrl":"https://doi.org/10.1111/febs.15741","url":null,"abstract":"Misfolding and aggregation of tau protein, into pathological amyloids, are hallmarks of a group of neurodegenerative diseases collectively termed tauopathies and their modulation may be therapeutically valuable. Herein, we describe the synthesis and characterization of a dopamine-based hybrid molecule, naphthoquinone-dopamine (NQDA). Using thioflavin S assay, CD, transmission electron microscopy, dynamic light scattering, Congo Red birefringence, and large unilamellar vesicle leakage assays, we demonstrated its efficacy in inhibiting the in vitro aggregation of key tau-derived amyloidogenic fragments, PHF6 (VQIVYK) and PHF6* (VQIINK), prime drivers of aggregation of full-length tau in disease pathology. Isothermal titration calorimetry analysis revealed that the interaction between NQDA and PHF6 is spontaneous and has significant binding efficiency driven by both entropic and enthalpic processes. Furthermore, NQDA efficiently disassembled preformed fibrils of PHF6 and PHF6* into nontoxic species. Molecular dynamic simulations supported the in vitro results and provided a plausible mode of binding of NQDA with PHF6 fibril. NQDA was also capable of inhibiting the aggregation of full-length tau protein and disrupting its preformed fibrils in vitro in a dose-dependent manner. In a comparative study, the IC50 value (50% inhibition of fibril formation) of NQDA in inhibiting the aggregation of PHF6 (25 µm) was ~ 17 µm, which is lower than for other bona fide amyloid inhibitors, naphthoquinone-tryptophan, rosmarinic acid, epigallocatechin gallate, ~ 21, ~ 77, or ~ 19 µm, respectively. Comparable superiority of NQDA was observed for inhibition of PHF6*. These findings suggest that NQDA can be a useful scaffold for designing new therapeutics for Alzheimer's disease and other tauopathies.","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 14","pages":"4267-4290"},"PeriodicalIF":5.4,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15741","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25318488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Author response for "Identification of a special cell type as a determinant of the kidney tropism of SARS‐CoV‐2" 作者对“鉴定一种特殊细胞类型作为SARS - CoV - 2嗜肾性的决定因素”的回应

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-06-09 DOI: 10.1111/febs.16114/v2/response1

Hongchun Lin, Xinxin Ma, Fang Xiao, H. Su, Yaling Shi, Yuntao Liu, Lan Song, Zhongde Zhang, Chun Zhang, Hui Peng

引用次数: 0

Author response for "Acetylation of the influenza A virus polymerase subunit PA in the N-terminal domain positively regulates its endonuclease activity" 作者对“甲型流感病毒n端聚合酶亚基PA的乙酰化正调控其内切酶活性”的回应

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-06-07 DOI: 10.1111/FEBS.16123/V2/RESPONSE1

D. Hatakeyama, M. Shoji, Seiryo Ogata, Takeshi Masuda, M. Nakano, Tsugunori Komatsu, A. Saitoh, Kyoko Makiyama, Hazuki Tsuneishi, Asuka Miyatake, Mizuki Takahira, Erin Nishikawa, A. Ohkubo, T. Noda, Y. Kawaoka, S. Ohtsuki, T. Kuzuhara

引用次数: 1

Review for "Identification of a small molecule splicing inhibitor targeting UHM domains" “靶向UHM结构域的小分子剪接抑制剂的鉴定”综述

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-05-23 DOI: 10.1111/febs.16199/v2/review1

H. Arthanari

引用次数: 0

Author response for "Resurrection and characterization of ancestral CYP11A1 enzymes" 作者对“祖先CYP11A1酶的复活和表征”的回应

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-05-22 DOI: 10.1111/FEBS.16054/V2/RESPONSE1

Philip Hartz, Silja J. Strohmaier, Basma M. EL‐Gayar, Ammar Abdulmughni, M. Hutter, F. Hannemann, E. Gillam, R. Bernhardt

引用次数: 0

Review for "Interaction mechanism of endogenous PP2A inhibitor protein ENSA with PP2A" 内源性PP2A抑制蛋白ENSA与PP2A相互作用机制综述

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-05-17 DOI: 10.1111/febs.16150/v1/review2

Miquel Pons

引用次数: 0

Review for "Conformational Switches and Redox Properties of the Colon Cancer‐Associated Human Lectin ZG16" 结肠癌相关人凝集素ZG16的构象开关和氧化还原特性综述

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-05-03 DOI: 10.1111/FEBS.16044/V1/REVIEW2

C. Rademacher

引用次数: 0

β-catenin regulates FOXP2 transcriptional activity via multiple binding sites. β-catenin通过多个结合位点调控FOXP2的转录活性。

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-05-01 Epub Date: 2020-12-26 DOI: 10.1111/febs.15656

Gesa Richter, Tianshu Gui, Benjamin Bourgeois, Chintan N Koyani, Peter Ulz, Ellen Heitzer, Dirk von Lewinski, Boudewijn M T Burgering, Ernst Malle, Tobias Madl

{"title":"β-catenin regulates FOXP2 transcriptional activity via multiple binding sites.","authors":"Gesa Richter, Tianshu Gui, Benjamin Bourgeois, Chintan N Koyani, Peter Ulz, Ellen Heitzer, Dirk von Lewinski, Boudewijn M T Burgering, Ernst Malle, Tobias Madl","doi":"10.1111/febs.15656","DOIUrl":"https://doi.org/10.1111/febs.15656","url":null,"abstract":"The transcription factor forkhead box protein P2 (FOXP2) is a highly conserved key regulator of embryonal development. The molecular mechanisms of how FOXP2 regulates embryonal development, however, remain elusive. Using RNA sequencing, we identified the Wnt signaling pathway as key target of FOXP2-dependent transcriptional regulation. Using cell-based assays, we show that FOXP2 transcriptional activity is regulated by the Wnt coregulator β-catenin and that β-catenin contacts multiple regions within FOXP2. Using nuclear magnetic resonance spectroscopy, we uncovered the molecular details of these interactions. β-catenin contacts a disordered FOXP2 region with α-helical propensity via its folded armadillo domain, whereas the intrinsically disordered β-catenin N terminus and C terminus bind to the conserved FOXP2 DNA-binding domain. Using RNA sequencing, we confirmed that β-catenin indeed regulates transcriptional activity of FOXP2 and that the FOXP2 α-helical motif acts as a key regulatory element of FOXP2 transcriptional activity. Taken together, our findings provide first insight into novel regulatory interactions and help to understand the intricate mechanisms of FOXP2 function and (mis)-regulation in embryonal development and human diseases. DATABASE: Expression data are available in the GEO database under the accession number GSE138938.","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 10","pages":"3261-3284"},"PeriodicalIF":5.4,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15656","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38682243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 8

Pathogenic postzygotic mosaicism in the tyrosine receptor kinase pathway: potential unidentified human disease hidden away in a few cells. 酪氨酸受体激酶通路中的致病性杂合子后嵌合：隐藏在少数细胞中的潜在不明人类疾病。

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-05-01 Epub Date: 2020-09-05 DOI: 10.1111/febs.15528

Irene Tiemann-Boege, Theresa Mair, Atena Yasari, Michal Zurovec

{"title":"Pathogenic postzygotic mosaicism in the tyrosine receptor kinase pathway: potential unidentified human disease hidden away in a few cells.","authors":"Irene Tiemann-Boege, Theresa Mair, Atena Yasari, Michal Zurovec","doi":"10.1111/febs.15528","DOIUrl":"10.1111/febs.15528","url":null,"abstract":"Mutations occurring during embryonic development affect only a subset of cells resulting in two or more distinct cell populations that are present at different levels, also known as postzygotic mosaicism (PZM). Although PZM is a common biological phenomenon, it is often overlooked as a source of disease due to the challenges associated with its detection and characterization, especially for very low-frequency variants. Moreover, PZM can cause a different phenotype compared to constitutional mutations. Especially, lethal mutations in receptor tyrosine kinase (RTK) pathway genes, which exist only in a mosaic state, can have completely new clinical manifestations and can look very different from the associated monogenic disorder. However, some key questions are still not addressed, such as the level of mosaicism resulting in a pathogenic phenotype and how the clinical outcome changes with the development and age. Addressing these questions is not trivial as we require methods with the sensitivity to capture some of these variants hidden away in very few cells. Recent ultra-accurate deep-sequencing approaches can now identify these low-level mosaics and will be central to understand systemic and local effects of mosaicism in the RTK pathway. The main focus of this review is to highlight the importance of low-level mosaics and the need to include their detection in studies of genomic variation associated with disease.","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 10","pages":"3108-3119"},"PeriodicalIF":5.4,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38275798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Cellular self-cannibalism helps immune cells fight the flu. 细胞自相残杀有助于免疫细胞对抗流感。

IF 5.4 2区生物学

FEBS Journal Pub Date : 2021-05-01 Epub Date: 2021-01-07 DOI: 10.1111/febs.15641

Joshua Luke Postoak, Guan Yang, Lan Wu, Luc Van Kaer

引用次数: 0