Abstract：
:Synapses are an early pathological target in many neurodegenerative diseases ranging from well-known adult onset conditions such as Alzheimer and Parkinson disease to neurodegenerative conditions of childhood such as spinal muscular atrophy (SMA) and neuronal ceroid lipofuscinosis (NCLs). However, the reasons why synapses are particularly vulnerable to such a broad range of neurodegeneration inducing stimuli remains unknown. To identify molecular modulators of synaptic stability and degeneration, we have used the Cln3 -/- mouse model of a juvenile form of NCL. We profiled and compared the molecular composition of anatomically-distinct, differentially-affected pre-synaptic populations from the Cln3 -/- mouse brain using proteomics followed by bioinformatic analyses. Identified protein candidates were then tested using a Drosophila CLN3 model to study their ability to modify the CLN3-neurodegenerative phenotype in vivo. We identified differential perturbations in a range of molecular cascades correlating with synaptic vulnerability, including valine catabolism and rho signalling pathways. Genetic and pharmacological targeting of key 'hub' proteins in such pathways was sufficient to modulate phenotypic presentation in a Drosophila CLN3 model. We propose that such a workflow provides a target rich method for the identification of novel disease regulators which could be applicable to the study of other conditions where appropriate models exist.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Llavero Hurtado M,Fuller HR,Wong AMS,Eaton SL,Gillingwater TH,Pennetta G,Cooper JD,Wishart TMdoi
10.1038/s41598-017-12603-0subject
Has Abstractpub_date
2017-09-29 00:00:00pages
12412issue
1issn
2045-2322pii
10.1038/s41598-017-12603-0journal_volume
7pub_type
杂志文章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：:It is believed that motor performance improves when individuals direct attention to movement outcome (external focus, EF) rather than to body movement itself (internal focus, IF). However, our previous study found that an optimal individual attentional strategy depended on motor imagery ability. We explored whether th...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep40592
更新日期：2017-01-17 00:00:00
abstract：:The serum macrophage inhibitory cytokine-1 (MIC-1) levels are elevated in some inflammatory conditions and cancers. We thus compared the levels of biliary and serum MIC-1 and conventional tumour markers between 23 biliary tract cancer (BTC) patients (malignant group) and 29 benign biliary disease patients (benign grou...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-09740-x
更新日期：2017-08-23 00:00:00
abstract：:After nearly a century of vaccination and six decades of drug therapy, tuberculosis (TB) kills more people annually than any other infectious disease. Substantial challenges to disease eradication remain among vulnerable and underserved populations. The Guarani-Kaiowá people are an indigenous population in Paraguay an...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-79621-3
更新日期：2021-01-13 00:00:00
abstract：:Risks threatening modern societies form an intricately interconnected network that often underlies crisis situations. Yet, little is known about how risk materializations in distinct domains influence each other. Here we present an approach in which expert assessments of likelihoods and influence of risks underlie a q...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep10998
更新日期：2015-06-18 00:00:00
abstract：:The previous performance of the English men's national football team in penalty shootouts has led to the widespread stereotype that English football players are particularly bad at scoring penalties. Research has proposed possible reasons behind this alleged "penalty curse". When looking at these reasons, the question...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-63889-6
更新日期：2020-04-27 00:00:00
abstract：:There is an urgent need for sensors deployed during focal therapies to inform treatment planning and in vivo monitoring in thin tissues. Specifically, the measurement of thermal properties, cooling surface contact, tissue thickness, blood flow and phase change with mm to sub mm accuracy are needed. As a proof of princ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep21395
更新日期：2016-02-26 00:00:00
abstract：:Previous studies have demonstrated that gestational diabetes mellitus (GDM) and Type 2 diabetes mellitus (T2D) share common genetic polymorphisms. We conducted meta-analysis and subgroup analysis of all available variants and determined the effects of confounding and experimental components on the genetic association ...
journal_title：Scientific reports
pub_type： 杂志文章,meta分析,评审
doi：10.1038/srep30539
更新日期：2016-07-29 00:00:00
abstract：:The current study aims to evaluate the burden of disease in Singapore by estimating the quality-adjusted life years (QALYs) lost due to mental disorders and chronic physical conditions. The second Singapore Mental Health Study (SMHS-2016) was conducted in 2016 among 6126 respondents aged 18 years and above. The World ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-59604-0
更新日期：2020-02-14 00:00:00
abstract：:To evaluate the performance of computed high b value diffusion-weighted images (DWI) in prostate cancer detection. 97 consecutive patients who had undergone multiparametric MRI of the prostate followed by biopsy were reviewed. Five radiologists independently scored 138 lesions on native high b-value images (b = 1200 s...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-21523-6
更新日期：2018-02-21 00:00:00
abstract：:Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since obesity leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation leads to early-onset o...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep24168
更新日期：2016-04-18 00:00:00
abstract：:Conventional crystalline β-MnO2 usually exhibits poor electrochemical activities due to the narrow tunnels in its rutile-type structure. In this study, we synthesized a novel 2D β-MnO2 network with long-range order assembled by β-MnO2 nanowires and demonstrated that the novel 2D β-MnO2 network exhibits enhanced electr...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep02193
更新日期：2013-01-01 00:00:00
abstract：:The lack of vaccines and antiviral treatment, along with the increasing number of cases of Zika virus (ZIKV) and Chikungunya virus (CHIKV) infections, emphasize the need for searching for new therapeutic strategies. In this context, the marine brown seaweed Canistrocarpus cervicornis has been proved to hold great anti...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-65357-7
更新日期：2020-05-19 00:00:00
abstract：:There is a growing appreciation for the diverse regulatory consequences of the family of proteins that bind to the secondary channel of E. coli RNA polymerase (RNAP), such as GreA, GreB or DksA. Similar binding sites could suggest a competition between them. GreA is characterised to rescue stalled RNAP complexes due t...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-73069-1
更新日期：2020-09-30 00:00:00
abstract：:Fibroblast growth factor-21 (FGF21) is closely related to various metabolic and cardiovascular disorders. However, the direct targets and mechanisms linking FGF21 to blood pressure control and hypertension are still elusive. Here we demonstrated a novel regulatory function of FGF21 in the baroreflex afferent pathway (...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep29582
更新日期：2016-07-08 00:00:00
abstract：:Sex-dependent effects of mismatched prenatal-postnatal maternal conditions are predicted by combining two evolutionary hypotheses: that foetal conditions provide a forecast of likely postnatal environments (Predictive Adaptive Response), and that the female foetus is better adapted than the male to maternal adversity ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-39513-7
更新日期：2019-02-21 00:00:00
abstract：:PP2A(Cdc55) is a highly conserved serine-threonine protein phosphatase that is involved in diverse cellular processes. In budding yeast, meiotic cells lacking PP2A(Cdc55) activity undergo a premature exit from meiosis I which results in a failure to form bipolar spindles and divide nuclei. This defect is largely due t...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep30397
更新日期：2016-07-26 00:00:00
abstract：:Current diagnostic tests for tuberculosis (TB) are not able to predict reactivation disease progression from latent TB infection (LTBI). The main barrier to predicting reactivation disease is the lack of our understanding of host biomarkers associated with progression from latent infection to active disease. Here, we ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-78793-2
更新日期：2020-12-16 00:00:00
abstract：:When we feel sad or depressed, our face invariably "drops". Conversely, when we try to cheer someone up, we might tell them "keep your smile up", so presupposing that modifying the configuration of their facial muscles will enhance their mood. A crucial assumption that underpins this hypothesis is that mental states a...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-48275-1
更新日期：2019-08-13 00:00:00
abstract：:Campylobacter hyointestinalis is a member of an emerging group of zoonotic Campylobacter spp. that are increasingly identified in both gastric and non-gastric disease in humans. Here, we discovered C. hyointestinalis in three separate classes of New Zealand ruminant livestock; cattle, sheep and deer. To investigate th...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-20889-x
更新日期：2018-02-05 00:00:00
abstract：:The ability to control the spatial distribution and temporal release of a therapeutic remains a central challenge for biomedical research. Here, we report the development and optimization of a novel substrate mediated therapeutic delivery system comprising of hyaluronic acid covalently functionalized liposomes (HALNPs...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep14683
更新日期：2015-10-01 00:00:00
abstract：:Oxidative stress (OS), mitochondrial dysfunction, and dysregulation of alpha-synuclein (aSyn) homeostasis are key pathogenic factors in Parkinson's disease. Nevertheless, the role of aSyn in mitochondrial physiology remains elusive. Thus, we addressed the impact of aSyn specifically on mitochondrial response to OS in ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep42942
更新日期：2017-02-22 00:00:00
abstract：:Inherited the advantages of inorganic salts and organic solvents, ionic liquids (ILs) exhibit many superior properties allowing them promising green solvents for the future. Although it has been widely acknowledged that the unique features of ILs originate from their dual ionic and organic nature, its microscopic phys...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep19644
更新日期：2016-01-19 00:00:00
abstract：:Floral transition is influenced by environmental factors such as light and temperature. Plants are capable of integrating photoperiod and ambient temperature signaling into their developmental program. Despite extensive investigations on individual genetic pathways, little is known about the molecular components that ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep12071
更新日期：2015-07-10 00:00:00
abstract：:The standardization of apiceutical products like as propolis extracts has been widely debated worldwide and variations in the propolis chemical composition are still very relevant topics for use-standardized of different propolis-type as medication by much of the world's population. The present manuscript discuss impo...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-54591-3
更新日期：2019-12-04 00:00:00
abstract：:The herbal medicine berberine (BBR) has been recently shown to be an AMP-activated protein kinase (AMPK) productive activator with various properties that induce anti-inflammatory responses. We investigated the effects of BBR on the mechanisms of mucosal CD4+T cell activation in vitro and on the inflammatory responses...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-48331-w
更新日期：2019-08-15 00:00:00
abstract：:Epidemiology of acute kidney injury (AKI) in developing countries is under-studied. We evaluated the risk and prognosis of AKI in patients admitted to intensive care units (ICUs) in Egypt. We recruited consecutive adults admitted to ICUs in Alexandria Teaching Hospitals over six months. We used the KDIGO criteria for ...
journal_title：Scientific reports
pub_type： 杂志文章,多中心研究
doi：10.1038/s41598-017-17264-7
更新日期：2017-12-07 00:00:00
abstract：:The prevalence of tobacco use in people with schizophrenia is much higher than in general population, which indicates a close relationship between nicotine addiction and schizophrenia. However, the molecular mechanism underlying the high comorbidity of tobacco smoking and schizophrenia remains largely unclear. In this...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-21297-x
更新日期：2018-02-13 00:00:00
abstract：:Membrane proteins are distinguished from soluble proteins by their insertion into biological membranes. This insertion is achieved via a noticeable arrangement of hydrophobic amino acids that are exposed at the surface of the protein, and renders the interaction with the aliphatic tails of lipids more energetically fa...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-17216-1
更新日期：2017-12-05 00:00:00
abstract：:The realization of reliable quantum channels, able to transfer a quantum state with high fidelity, is a fundamental step in the construction of scalable quantum devices. In this paper we describe a transmission scheme based on the genuinely quantum effect known as Bloch oscillations. The proposed protocol makes it pos...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep26054
更新日期：2016-05-18 00:00:00
