Abstract:
:Alzheimer's disease (AD) is characterized by excessive production and deposition of amyloid-beta (Aβ) proteins as well as synapse dysfunction and loss. While soluble Aβ oligomers (AβOs) have deleterious effects on synapse function and reduce synapse number, the underlying molecular mechanisms are not well understood. Here we screened synaptic organizer proteins for cell-surface interaction with AβOs and identified a novel interaction between neurexins (NRXs) and AβOs. AβOs bind to NRXs via the N-terminal histidine-rich domain (HRD) of β-NRX1/2/3 and alternatively-spliced inserts at splicing site 4 of NRX1/2. In artificial synapse-formation assays, AβOs diminish excitatory presynaptic differentiation induced by NRX-interacting proteins including neuroligin1/2 (NLG1/2) and the leucine-rich repeat transmembrane protein LRRTM2. Although AβOs do not interfere with the binding of NRX1β to NLG1 or LRRTM2, time-lapse imaging revealed that AβO treatment reduces surface expression of NRX1β on axons and that this reduction depends on the NRX1β HRD. In transgenic mice expressing mutated human amyloid precursor protein, synaptic expression of β-NRXs, but not α-NRXs, decreases. Thus our data indicate that AβOs interact with NRXs and that this interaction inhibits NRX-mediated presynaptic differentiation by reducing surface expression of axonal β-NRXs, providing molecular and mechanistic insights into how AβOs lead to synaptic pathology in AD.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Naito Y,Tanabe Y,Lee AK,Hamel E,Takahashi Hdoi
10.1038/srep42548subject
Has Abstractpub_date
2017-02-13 00:00:00pages
42548issn
2045-2322pii
srep42548journal_volume
7pub_type
杂志文章abstract::An accurate prediction of the outcome of a given drug treatment requires quantitative values for all parameters and concentrations involved as well as a detailed characterization of the network of interactions where the target molecule is embedded. Here, we present a high-throughput in silico screening of all potentia...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-30913-9
更新日期:2018-08-21 00:00:00
abstract::Animals have evolved limb proportions adapted to different environments, but it is not yet clear to what extent these proportions are directly influenced by the environment during prenatal development. The developing skeleton experiences mechanical loading resulting from embryo movement. We tested the hypothesis that ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep41926
更新日期:2017-02-06 00:00:00
abstract::In contrast to mild infections of Group A Streptococcus (GAS) invasive infections of GAS still pose a serious health hazard: GAS disseminates from sterile sites into the blood stream or deep tissues and causes sepsis or necrotizing fasciitis. In this case antibiotics do not provide an effective cure as the bacteria ar...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-11276-z
更新日期:2017-09-18 00:00:00
abstract::Rapid histopathological evaluation of fresh, unfixed human tissue using optical sectioning microscopy would have applications to intraoperative surgical margin assessment. Microscopy with ultraviolet surface excitation (MUSE) is a low-cost optical sectioning technique using ultraviolet illumination which limits fluore...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-22264-2
更新日期:2018-03-14 00:00:00
abstract::Silicon, the workhorse of semiconductor industry, is being exploited for various functional applications in numerous fields of nanotechnology. In this paper, we report the fabrication of depth controllable amorphous silicon (a-Si) layers under 80 keV Ar+ ion sputtering at off-normal ion incidences of 30°, 40° and 50° ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-68873-8
更新日期:2020-07-17 00:00:00
abstract::Perovskite solar cells based on series of inorganic cesium lead bromide and iodide mixture, CsPbBr3-xI x , where x varies between 0, 0.1, 0.2, and 0.3 molar ratio were synthesized by two step-sequential deposition at ambient condition to design the variations of wide band gap light absorbers. A device with high overal...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-20228-0
更新日期:2018-02-06 00:00:00
abstract::Definitive evidence for the direct band gap predicted for Wurtzite Gallium Phosphide (WZ GaP) nanowires has remained elusive due to the lack of strong band-to-band luminescence in these materials. In order to circumvent this problem, we successfully obtained large volume WZ GaP structures grown by nanoparticle-crawlin...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-64809-4
更新日期:2020-05-13 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive and lethal malignancies. Long non-coding RNAs (lncRNAs) are a novel class of non-protein-coding transcripts that have been implicated in cancer biogenesis and prognosis. By repurposing microarray probes, we herein analysed the lncRNA expression...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep33535
更新日期:2016-09-15 00:00:00
abstract::Site variation in fixation, staining, and scanning can confound automated tissue based image classifiers for disease characterization. In this study we incorporated stability into four feature selection methods for identifying the most robust and discriminating features for two prostate histopathology classification t...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-33026-5
更新日期:2018-10-08 00:00:00
abstract::Algicidal microbes could effectively remove the harmful algae from the waters. In this study, we were concerned with the ecological influence of an algicide extracted from Streptomyces alboflavus RPS, which could completely lyse the Phaeocystis globosa cells within two days. In microcosms, 4 μg/mL of the microbial alg...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep20081
更新日期:2016-02-05 00:00:00
abstract::Activated coke (AC) has great potential in the field of low-temperature NO removal (DeNOx), especially the branch prepared by blending modification. In this study, the AC-based pyrolusite and/or titanium ore blended catalysts were prepared and applied for DeNOx. The results show blending pyrolusite and titanium ore pr...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-76592-3
更新日期:2020-11-10 00:00:00
abstract::Features of sleep were shown to reflect aging, typical sex differences and cognitive abilities of humans. However, these measures are characterized by redundancy and arbitrariness. Our present approach relies on the assumptions that the spontaneous human brain activity as reflected by the scalp-derived electroencephal...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-021-81230-7
更新日期:2021-01-21 00:00:00
abstract::Knowledge of the structure-property-function relationship of humic substances (HSs) is key for understanding their role in soil. Despite progress, studies on this topic are still under discussion. We analyzed 37 humic fractions with respect to their isotopic composition, structural characteristics, and properties resp...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep20798
更新日期:2016-02-10 00:00:00
abstract::Although attempts have been made to reveal the relationships between bacteria and human health, little is known about the species and function of the microbial community associated with oral diseases. In this study, we report the sequencing of 16 metagenomic samples collected from dental swabs and plaques representing...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep01843
更新日期:2013-01-01 00:00:00
abstract::Co-existing infection/inflammation and birth asphyxia potentiate the risk of developing neonatal encephalopathy (NE) and adverse outcome. In a newborn piglet model we assessed the effect of E. coli lipopolysaccharide (LPS) infusion started 4 h prior to and continued for 48 h after hypoxia on brain cell death and syste...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-46488-y
更新日期:2019-07-15 00:00:00
abstract::The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malign...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep12083
更新日期:2015-07-13 00:00:00
abstract::Microstructures in nature are ultrafine and ordered in biological roles, which have attracted material scientists. Spirulina forms three-dimensional helical microstructure, one of remarkable features in nature beyond our current processing technology such as lithography in terms of mass-productivity and structural mul...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep04919
更新日期:2014-05-12 00:00:00
abstract::Mesoporous silica is an emerging technology to solve problems of existing and to support projected revolutionary applications ranging from targeted drug delivery to artificial kidney. However, one of the major driving mechanisms, electric charging of internal mesoporous surfaces, has not been characterized yet. In the...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-36487-w
更新日期:2019-01-15 00:00:00
abstract::Dramatic functional changes of enzyme usually require scores of alterations in amino acid sequence. However, in the case of guanylate kinase (GK), the functional novelty is induced by a single (S→P) mutation, leading to the functional transition of the enzyme from a phosphoryl transfer kinase into a phosphorprotein in...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep08405
更新日期:2015-02-12 00:00:00
abstract::The discovery of novel ligand chemotypes allows to explore uncharted regions in chemical space, thereby potentially improving synthetic accessibility, potency, and the drug-likeness of molecules. Here, we demonstrate the scaffold-hopping ability of the new Weighted Holistic Atom Localization and Entity Shape (WHALES) ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-34677-0
更新日期:2018-11-07 00:00:00
abstract::Jasmonates (JAs) are plant-specific key signaling molecules that respond to various stimuli and are involved in the synthesis of secondary metabolites. However, little is known about the JA signal pathway, especially in economically significant medicinal plants. To determine the functions of novel genes that participa...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep14048
更新日期:2015-09-21 00:00:00
abstract::We introduce a simple criterion to identify two-dimensional (2D) materials based on the comparison between experimental lattice constants and lattice constants mainly obtained from Materials-Project (MP) density functional theory (DFT) calculation repository. Specifically, if the relative difference between the two la...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-05402-0
更新日期:2017-07-12 00:00:00
abstract::Quantum coherence is one of the old but always important concepts in quantum mechanics, and now it has been regarded as a necessary resource for quantum information processing and quantum metrology. However, the question of how to quantify the quantum coherence has just been paid the attention recently (see, e.g., Bau...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-15323-7
更新日期:2017-11-14 00:00:00
abstract::Zeolites/molecular sieves with uniform, molecular-sized pores are important for many adsorption-based separation processes. Pore size gaps, however, exist in the current zeolite family. This leads to a great challenge of separating molecules with size differences at ~0.01 nm level. Here, we report a novel concept, por...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep13981
更新日期:2015-09-11 00:00:00
abstract::Mitochondria behave as functional and structural hubs for innate defense against intracellular infection. While the mitochondrial membrane serves as a platform for the assembly of signaling complexes activated by intracellular infection, various danger molecules derived from impaired mitochondria activate innate signa...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-68053-8
更新日期:2020-07-07 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-020-59779-6
更新日期:2020-03-16 00:00:00
abstract::Disc degeneration (DD) is a multifaceted chronic process that alters the structure and function of intervertebral discs. The pathophysiology of degeneration is not completely understood, but the consensus is that changes in genes encoding extracellular matrix (ECM) proteins in the disc are the leading factors contribu...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-04384-3
更新日期:2017-06-23 00:00:00
abstract::Current and expected changes in global climate are major threat for biological diversity affecting individuals, communities and ecosystems. However, there is no general trend in the plants response to the climate change. The aim of present study was to evaluate impact of the future climate changes on the distribution ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-13088-7
更新日期:2017-10-05 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-020-57833-x
更新日期:2020-01-15 00:00:00
abstract::Developing an alternative method for fabricating microscale graphene patterns that overcomes the obstacles of organic contamination, linewidth resolution, and substrate damaging is paramount for applications in optoelectronics. Here we propose to pattern chemical vapor deposition grown graphene film through a stencil ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep46583
更新日期:2017-04-19 00:00:00