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https://www.readbyqxmd.com/read/28520620/-epigallocatechin-3-gallate-ameliorates-memory-impairment-and-rescues-the-abnormal-synaptic-protein-levels-in-the-frontal-cortex-and-hippocampus-in-a-mouse-model-of-alzheimer-s-disease
#1
Yufang Guo, Yan Zhao, Ying Nan, Xiang Wang, Yulong Chen, Shuang Wang
(-)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenolic extract in green tea and it has attracted increasing attention for its multiple bioactive effects. However, the mechanisms by which EGCG exerts its neuroprotective actions in Alzheimer's disease (AD) are presently lacking. In the present study, a sporadic AD transgenic mouse model known as senescence-accelerated mouse prone 8 (SAMP8) was used to investigate whether oral administration of EGCG could improve recognition and memory function through reduction of amyloid β (Aβ) and tau hyperphosphorylation...
May 17, 2017: Neuroreport
https://www.readbyqxmd.com/read/28505196/unveiling-a-novel-transient-druggable-pocket-in-bace-1-through-molecular-simulations-conformational-analysis-and-binding-mode-of-multisite-inhibitors
#2
Ornella Di Pietro, Jordi Juárez-Jiménez, Diego Muñoz-Torrero, Charles A Laughton, F Javier Luque
The critical role of BACE-1 in the formation of neurotoxic ß-amyloid peptides in the brain makes it an attractive target for an efficacious treatment of Alzheimer's disease. However, the development of clinically useful BACE-1 inhibitors has proven to be extremely challenging. In this study we examine the binding mode of a novel potent inhibitor (compound 1, with IC50 80 nM) designed by synergistic combination of two fragments-huprine and rhein-that individually are endowed with very low activity against BACE-1...
2017: PloS One
https://www.readbyqxmd.com/read/28499972/simvastatin-ameliorates-memory-impairment-and-neurotoxicity-in-streptozotocin-induced-diabetic-mice
#3
Shun-Chang Fang, Hang Xie, Fang Chen, Mei Hu, Yan Long, Hong-Bin Sun, Ling-Yi Kong, Hao Hong, Su-Su Tang
Diabetes comes with an additional burden of moderate to severe hyperlipidemia, but little is known about the effects of lipid-lowering therapy on diabetic complications such as diabetes-associated cognitive decline. Herein we investigated the effects of statins on memory impairment and neurotoxicity in streptozotocin-induced diabetic mice. Our data indicated that oral administration of simvastatin at 10 or 20mg/kg for 4weeks significantly ameliorated diabetes-associated memory impairment reflected by performance better in the Morris water maze and Y-maze tests...
May 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28469554/physiological-functions-of-the-%C3%AE-site-amyloid-precursor-protein-cleaving-enzyme-1-and-2
#4
REVIEW
Riqiang Yan
BACE1 was discovered as the β-secretase for initiating the cleavage of amyloid precursor protein (APP) at the β-secretase site, while its close homology BACE2 cleaves APP within the β-amyloid (Aβ) domain region and shows distinct cleavage preferences in vivo. Inhibition of BACE1 proteolytic activity has been confirmed to decrease Aβ generation and amyloid deposition, and thus specific inhibition of BACE1 by small molecules is a current focus for Alzheimer's disease therapy. While BACE1 inhibitors are being tested in advanced clinical trials, knowledge regarding the properties and physiological functions of BACE is highly important and this review summarizes advancements in BACE1 research over the past several years...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28460142/comparative-proteomics-reveals-silver-nanoparticles-alter-fatty-acid-metabolism-and-amyloid-beta-clearance-for-neuronal-apoptosis-in-a-triple-cell-co-culture-model-of-the-blood-brain-barrier
#5
Ho-Chen Lin, Ming-Yi Ho, Chao-Ming Tsen, Chien-Chu Huang, Chin-Ching Wu, Yuh-Jeen Huang, I-Lun Hsiao, Chun-Yu Chuang
Silver nanoparticles (AgNPs) enter the central nervous system through the blood-brain barrier (BBB). AgNP exposure can increase amyloid beta (Aβ) deposition in neuronal cells to potentially induce Alzheimer disease (AD) progression. However, the mechanism through which AgNPs alter BBB permeability in endothelial cells and subsequently lead to AD progression remains unclear. This study investigated whether AgNPs disrupt the tight junction proteins of brain endothelial cells, and alter the proteomic metabolism of neuronal cells underlying AD progression in a triple cell co-culture model constructed using mouse brain endothelial (bEnd...
April 29, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28450540/aplp1-is-a-synaptic-cell-adhesion-molecule-supporting-maintenance-of-dendritic-spines-and-basal-synaptic-transmission
#6
Sandra Schilling, Annika Mehr, Susann Ludewig, Jonathan Stephan, Marius Zimmermann, Alexander August, Paul Strecker, Martin Korte, Edward H Koo, Ulrike Müller, Stefan Kins, Simone Eggert
The amyloid precursor protein (APP), a key player in Alzheimer's disease, belongs to the family of synaptic adhesion molecules (SAM's) due to its impact on synapse formation and synaptic plasticity. These functions are mediated by both, the secreted ectodomain (sAPP) that acts as a neurotrophic factor and full-length APP forming trans-cellular dimers. Two homologues of APP exist in mammals, the APP like proteins, APLP1 and APLP2, exhibiting partly overlapping functions to APP. Here we tested if APLP1 and APLP2 also show features of SAMs...
April 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28432142/structural-similarities-between-neuregulin-1-3-isoforms-determine-their-subcellular-distribution-and-signaling-mode-in-central-neurons
#7
Detlef Vullhorst, Tanveer Ahmad, Irina Karavanova, Carolyn Keating, Andres Buonanno
The Neuregulin (NRG) family of ErbB ligands is comprised of numerous variants originating from the use of different genes, alternative promoters and splice variants. NRGs have generally been thought to be transported to axons and presynaptic terminals where they signal via ErbB3/4 receptors in paracrine or juxtacrine mode. However, we recently demonstrated that unprocessed pro-NRG2 accumulates on cell bodies and proximal dendrites, and that NMDAR activity is required for shedding of its ectodomain by metalloproteinases...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28427814/design-synthesis-and-x-ray-structural-studies-of-bace-1-inhibitors-containing-substituted-2-oxopiperazines-as-p1-p2-ligands
#8
Arun K Ghosh, Margherita Brindisi, Yu-Chen Yen, Emilio L Cárdenas, Jean-Rene Ella-Menye, Nagaswamy Kumaragurubaran, Xiangping Huang, Jordan Tang, Andrew D Mesecar
We report the design and synthesis of a series of BACE1 inhibitors incorporating mono- and bicyclic 6-substituted 2-oxopiperazines as novel P1' and P2' ligands and isophthalamide derivative as P2-P3 ligands. Among mono-substituted 2-oxopiperazines, inhibitor 5a with N-benzyl-2-oxopiperazine and isophthalamide showed potent BACE1 inhibitory activity (Ki=2nM). Inhibitor 5g, with N-benzyl-2-oxopiperazine and substituted indole-derived P2-ligand showed a reduction in potency. The X-ray crystal structure of 5g-bound BACE1 was determined and used to design a set of disubstituted 2-oxopiperazines and bicyclic derivatives that were subsequently investigated...
April 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28427163/the-application-of-is6110-baced-loop-mediated-isothermal-amplification-lamp-in-the-early-diagnosis-of-tuberculous-meningitis
#9
Wen-Wen Sun, Qin Sun, Li-Ping Yan, Qing Zhang
Here, we evaluated the potential activity of rapid Mycobacterium tuberculosis detection with loop-mediated isothermal amplification (LAMP), for the early diagnosis of tuberculous meningitis (TBM). Patients with suspected TBM from January 2014 to December 2015 were reviewed retrospectively. The cerebrospinalfluid(CSF) was collected. Acid-fast bacillus (AFB) staining, MGIT 960 culture, real-time fluorescent quantitative polymerase chain reaction (RTFQ PCR) and LAMP were performed. A total of 200 patients were included in the study...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413992/screening-and-elucidation-of-selected-natural-compounds-for-anti-alzheimer-s-potential-targeting-bace-1-enzyme-a-case-computational-study
#10
Syed Sayeed Ahmad, Salman Akhtar, Syed Mohd Danish Rizvi, Mohammad A Kamal, Usman Sayeed, Mohd Kalim A Khan, Mohd Haris Siddiqui, Jamal M Arif
BACKGROUND: The present study clarifies the molecular interactions of human BACE1 with novel natural ligands and also with the well-known ligand 2, 2, 4-trihydroxychalcone and Galangin for comparison. OBJECTIVE: The study of enzyme- ligands interaction is interest, description of ligands binding to the active site of target molecule could be beneficial to better understanding the mechanism of the ligand on the target molecule. METHOD: Lipinski rule of five, and docking study was performed between ligands and enzyme using 'Autodock4...
April 14, 2017: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/28403230/isoflurane-anesthesia-promotes-cognitive-impairment-by-inducing-expression-of-%C3%AE-amyloid-protein-related-factors-in-the-hippocampus-of-aged-rats
#11
Shuai Zhang, Xueyuan Hu, Wei Guan, Li Luan, Bei Li, Qichao Tang, Honggang Fan
Isoflurane anesthesia has been shown to be responsible for cognitive impairment in Alzheimer's disease (AD) and development of AD in the older age groups. However, the pathogenesis of AD-related cognitive impairments induced by isoflurane anesthesia remains elusive. Thus, this study was designed to investigate the mechanism by which isoflurane anesthesia caused AD-related cognitive impairments. Aged Wistar rats were randomly divided into 6 groups (n = 12), 1 control group (CONT) and 5 isoflurane treated (ISO) groups (ISO 0, ISO 0...
2017: PloS One
https://www.readbyqxmd.com/read/28382866/dynamic-simulation-docking-and-dft-studies-applied-to-a-set-of-anti-acetylcholinesterase-inhibitors-in-the-enzyme-%C3%AE-secretase-bace-1-an-important-therapeutic-target-in-alzheimer-s-disease
#12
Edeildo F Silva-Júnior, Paulo H Barcellos França, Lucindo José Quintas-Júnior, Francisco J B Mendonça-Junior, Luciana Scotti, Marcus T Scotti, Thiago Mendonça de Aquino, João Xavier Araújo-Júnior
BACKGROUND: Alzheimer's disease (AD) affects mainly elderly people over 60 years of age. Currently, there are more than 35 million people with this disease worldwide. The enzyme β-secretase is involved in the processing of the amyloid precursor protein and plays a key role in the physiopathology of AD. The action of some acetylcholinesterase inhibitors (AChEI) as β-secretase inhibitors has been reported. OBJECTIVE: The aim of this study was to highlight the modes of the binding of acetylcholinesterase ligands onto the active site of the β-secretase enzyme...
April 6, 2017: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/28296815/anterior-trunk-mobility-does-not-predict-disability-in-elderly-women-with-acute-low-back-pain-brazilian-back-complaints-in-the-elders-bace-brazil-study-results
#13
Diogo Carvalho Felicio, Daniele Sirineu Pereira, Juliano Bergamaschine Mata Diz, Barbara Zille de Queiroz, Juscelio Pereira da Silva, Amanda Aparecida Oliveira Leopoldino, Leani Souza Maximo Pereira
STUDY DESIGN: Cross-sectional, ancillary study of an international multicenter epidemiological study. OBJECTIVE: To investigate the relationship of the anterior trunk mobility with self-report and physical performance measures in elderly women with acute low back pain (LBP). SUMMARY OF BACKGROUND DATA: LBP is one of the most prevalent pain complaints in the elderly population. It is postulated that the increased range of motion (ROM) of limited joints of the trunk may improve LBP and functionality of patients...
March 14, 2017: Spine
https://www.readbyqxmd.com/read/28254759/autophagosomes-cooperate-in-the-degradation-of-intracellular-c-terminal-fragments-of-the-amyloid-precursor-protein-via-the-mvb-lysosomal-pathway
#14
Alexis E González, Vanessa C Muñoz, Viviana A Cavieres, Hianara A Bustamante, Víctor-Hugo Cornejo, Yunan C Januário, Ibeth González, Claudio Hetz, Luis L daSilva, Alejandro Rojas-Fernández, Ronald T Hay, Gonzalo A Mardones, Patricia V Burgos
Brain regions affected by Alzheimer disease (AD) display well-recognized early neuropathologic features in the endolysosomal and autophagy systems of neurons, including enlargement of endosomal compartments, progressive accumulation of autophagic vacuoles, and lysosomal dysfunction. Although the primary causes of these disturbances are still under investigation, a growing body of evidence suggests that the amyloid precursor protein (APP) intracellular C-terminal fragment β (C99), generated by cleavage of APP by β-site APP cleaving enzyme 1 (BACE-1), is the primary cause of the endosome enlargement in AD and the earliest initiator of synaptic plasticity and long-term memory impairment...
March 2, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28250013/time-variant-genetic-effects-as-a-cause-for-preterm-birth-insights-from-a-population-of-maternal-cousins-in-sweden
#15
Julius Juodakis, Jonas Bacelis, Ge Zhang, Louis J Muglia, Bo Jacobsson
Preterm delivery (PTD) is the leading cause of neonatal mortality worldwide, yet its etiology remains largely unexplained. We propose that the genetic factors controlling this trait could act in a nonuniform manner during pregnancy, with each factor having a unique "window of sensitivity." We test this hypothesis by modeling the distribution of gestational ages (GAs) observed in maternal cousins from the Swedish Medical Birth Register (MBR) (n = 35,541 pairs). The models were built using a time-to-event framework, with simulated genetic factors that increase the hazard of birth either uniformly across the pregnancy (constant effect) or only in particular windows (varying effect)...
April 3, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28249241/biophenols-pharmacology-against-the-amyloidogenic-activity-in-alzheimer-s-disease
#16
REVIEW
Syed Haris Omar
Alzheimer's disease characterized by misfolding, aggregation, and accumulation of amyloid fibrils in an insoluble form in the brain, is often known as amyloidosis. The process of aggregation follows a mechanism of seeded polymerization. For decades, a great number of failures in Alzheimer's disease (AD) drug development, with both small molecules and immunotherapies failing to establish a drug/placebo difference or having an unacceptable toxicity have led to the therapeutic research interest towards a group of anti-amyloidogenic compounds originated from plants called biophenols...
May 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28248932/bace-inhibitor-bust-in-alzheimer-trial
#17
Asher Mullard
No abstract text is available yet for this article.
March 1, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28203608/modeling-fragile-x-syndrome-in-neurogenesis-an-unexpected-phenotype-and-a-novel-tool-for-future-therapies
#18
Barbara Bardoni, Maria Capovilla, Enzo Lalli
FMRP is an RNA-binding protein involved in synaptic translation. Its absence causes a form of intellectual disability, the Fragile X syndrome (FXS). Small neuroanatomical abnormalities, present both in human and mouse FMRP-deficient brains, suggest a subtle critical role of this protein in neurogenesis. Stable depletion of FMRP has been obtained in a mouse embryonic stem cell line Fmr1 (shFmr1 ES) that does not display morphological alterations, but an abnormal expression of a subset of genes mainly involved in neuronal differentiation and maturation...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28188785/sortilin-related-receptor-1-interacts-with-amyloid-precursor-protein-and-is-activated-by-6-shogaol-leading-to-inhibition-of-the-amyloidogenic-pathway
#19
Ji-Young Na, Kibbeum Song, Ju-Woon Lee, Sokho Kim, Jungkee Kwon
Sortilin-related receptor 1 (SORL1) is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate amyloid beta (Aβ). Although 6-shogaol, a constituent of ginger, has been reported to have anti-inflammatory and anti-oxidant effects on neuronal cells, research regarding the activation of SORL1 has not yet been reported. Here, we aimed to investigate whether 6-shogaol contributes to the increases in SORL1 that are related to Alzheimer's disease (AD). To clarify the effect of 6-shogaol as a possible activator of SORL1, we used SORL1 siRNA as a blockade of SORL1 in hippocampal neuronal cells (HT22)...
February 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28173812/anthocyanins-encapsulated-by-plga-peg-nanoparticles-potentially-improved-its-free-radical-scavenging-capabilities-via-p38-jnk-pathway-against-a%C3%AE-1-42-induced-oxidative-stress
#20
Faiz Ul Amin, Shahid Ali Shah, Haroon Badshah, Mehtab Khan, Myeong Ok Kim
BACKGROUND: In order to increase the bioavailability of hydrophilic unstable drugs like anthocyanins, we employed a polymer-based nanoparticles approach due to its unique properties such as high stability, improved bioavailability and high water-soluble drug loading efficiency. Anthocyanins constitute a subfamily of flavonoids that possess anti-oxidative, anti-inflammatory and neuroprotective properties. However, anthocyanins are unstable because their phenolic hydroxyl groups are easily oxidized into quinones, causing a reduced biological activity...
February 7, 2017: Journal of Nanobiotechnology
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