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https://www.readbyqxmd.com/read/28223223/berberine-improves-cognitive-impairment-by-promoting-autophagic-clearance-and-inhibiting-production-of-%C3%AE-amyloid-in-app-tau-ps1-mouse-model-of-alzheimer-s-disease
#1
Min Huang, Xin Jiang, Yubin Liang, Qiong Liu, Siyan Chen, Yi Guo
This study investigates the neuroprotective properties of berberine (a natural isoquinoline alkaloid isolated from the Rhizoma coptidis) and finds that berberine could promote β-amyloid (Aβ) clearance and inhibit Aβ production in the triple-transgenic mouse model of Alzheimer's disease (3×Tg-AD). During the study, berberine was first administrated to treat 3×Tg-AD mice and primary neurons. Morris water maze assay, western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining and histological analysis, transmission electron microscopic analysis were then used to evaluate the effects of the berberine administration...
February 20, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28219697/effect-of-salvia-miltiorrhiza-root-extract-on-brain-acetylcholinesterase-and-butyrylcholinesterase-activities-their-mrna-levels-and-memory-evaluation-in-rats
#2
Marcin Ozarowski, Przemyslaw L Mikolajczak, Anna Piasecka, Radoslaw Kujawski, Joanna Bartkowiak-Wieczorek, Anna Bogacz, Michal Szulc, Ewa Kaminska, Malgorzata Kujawska, Agnieszka Gryszczynska, Piotr Kachlicki, Waldemar Buchwald, Andrzej Klejewski, Agnieszka Seremak-Mrozikiewicz
Salvia miltiorrhiza (Lamiaceae), one of the most important and popular plants of traditional medicine of Asia, is used for the prevention and treatment of cardiovascular diseases and in central nervous system disturbances. The main aim of this study was to assess the influence of subchronic (28-fold) administration of Salvia miltiorrhiza root extract (SE, 200mg/kg, p.o.) on behavioural activity and memory of rats and to evaluate the activities of cholinesterases (AChE and BuChE) and gene expression levels of AChE and BuChE as well as of beta-secretase (BACE1) in the hippocampus and frontal cortex in vivo...
February 17, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28191691/bace1-regulates-the-proliferation-and-cellular-functions-of-schwann-cells
#3
Xiangyou Hu, Hailong Hou, Chinthasagar Bastian, Wanxia He, Shupeng Qiu, Yingying Ge, Xinhua Yin, Grahame J Kidd, Sylvain Brunet, Bruce D Trapp, Selva Baltan, Riqiang Yan
BACE1 is an indispensable enzyme for generating β-amyloid peptides, which are excessively accumulated in brains of Alzheimer's patients. However, BACE1 is also required for proper myelination of peripheral nerves, as BACE1-null mice display hypomyelination. To determine the precise effects of BACE1 on myelination, here we have uncovered a role of BACE1 in the control of Schwann cell proliferation during development. We demonstrate that BACE1 regulates the cleavage of Jagged-1 and Delta-1, two membrane-bound ligands of Notch...
February 13, 2017: Glia
https://www.readbyqxmd.com/read/28176624/vitamin-d-combined-with-resveratrol-prevents-cognitive-decline-in-samp8-mice
#4
Jinbo Cheng, Yehua Rui, Liqiang Qin, Jiaying Xu, Shufen Han, Linxi Yuan, Xuebin Yin, Zhongxiao Wan
Background Vitamin D (VD) and resveratrol (RSV) are two nutritional molecules that have reported neuroprotective effects, and findings from cellular models suggest that resveratrol could potentiate vitamin D's effects. The senescence-accelerated mouse-prone 8 (SAMP8) is a useful model of Alzheimer's disease (AD)-related memory impairment. Objective We aimed to explore how the combination of vitamin D with resveratrol would affect memory impairments shown by SAMP8 mice, as well as the potential mechanisms...
February 6, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28159908/regulation-of-synaptic-a%C3%AE-generation-through-bace1-retrograde-transport-in-a-mouse-model-of-alzheimer-s-disease
#5
Xuan Ye, Tuancheng Feng, Prasad Tammineni, Qing Chang, Yu Young Jeong, David J Margolis, Huaibin Cai, Alexander Kusnecov, Qian Cai
: β-amyloid (Aβ) peptides play a key role in synaptic damage and memory deficits in the early pathogenesis of Alzheimer's disease (AD). Abnormal accumulation of Aβ at nerve terminals leads to synaptic pathology and ultimately to neurodegeneration. β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the major neuronal β-secretase for Aβ generation. However, the mechanisms regulating BACE1 distribution in axons and β cleavage of APP at synapses remain largely unknown...
February 3, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28158647/increased-bace1-as-long-noncoding-rna-and-%C3%AE-amyloid-levels-in-heart-failure
#6
Simona Greco, Germana Zaccagnini, Paola Fuschi, Christine Voellenkle, Matteo Carrara, Iman Sadeghi, Claudia Bearzi, Biagina Maimone, Serenella Castelvecchio, Konstantinos Stellos, Carlo Gaetano, Lorenzo Menicanti, Fabio Martelli
No abstract text is available yet for this article.
February 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28157093/bace1-dynamics-upon-inhibition-with-a-bace-inhibitor-and-correlation-to-downstream-alzheimer-s-disease-markers-in-elderly-healthy-participants
#7
Maarten Timmers, Soraia Barão, Bianca Van Broeck, Ina Tesseur, John Slemmon, Katja De Waepenaert, Jennifer Bogert, Leslie M Shaw, Sebastiaan Engelborghs, Dieder Moechars, Marc Mercken, Luc Van Nueten, Luc Tritsmans, Bart de Strooper, Johannes Rolf Streffer
The β-site amyloid-β protein precursor (AβPP) cleaving enzyme-1 (BACE1) is the rate limiting enzyme in the generation of amyloid-β peptide (Aβ) from AβPP, one of the major pathways in Alzheimer's disease (AD) pathology. Increased BACE1 levels and activity have been reported in the brain of patients with sporadic AD. Therefore, changes of BACE1 levels in the cerebrospinal fluid (CSF) have also been investigated as a possible biomarker of the disease. We analyzed BACE1 levels in CSF of elderly healthy participants before and after chronic treatment with a BACE inhibitor (BACEi) and evaluated the correlation between BACE1 levels and downstream AD markers...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28153449/a-capillary-electrophoresis-mass-spectrometry-based-method-for-the-screening-of-%C3%AE-secretase-inhibitors-as-potential-alzheimer-s-disease-therapeutics
#8
Jan Schejbal, Lucie Slezáčková, Roman Řemínek, Zdeněk Glatz
In this work a novel capillary electrophoresis-mass spectrometry (CE-MS) based method was developed and validated for the assay of β-secretase (BACE1) activity as a potential target for Alzheimer's disease (AD) treatment. In contrast with the typically used Förster resonance energy transfer (FRET) assays, an unlabelled decapeptide derived from the amyloid precursor protein BACE1 site with the "Swedish mutation" was used as the substrate. The CE usage enabled the enzymatic reaction to be carried out in as small a volume as 100μL in 60min with sufficient yields of proteolytic product, which was subsequently separated in a bare fused silica capillary using 12...
March 3, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28145081/chronic-sleep-restriction-induces-cognitive-deficits-and-cortical-beta-amyloid-deposition-in-mice-via-bace1-antisense-activation
#9
Hong-Yi Zhao, Hui-Juan Wu, Jia-Lin He, Jian-Hua Zhuang, Zhen-Yu Liu, Liu-Qing Huang, Zhong-Xin Zhao
AIMS: To clarify the correlation between chronic sleep restriction (CSR) and sporadic Alzheimer disease (AD), we determined in wild-type mice the impact of CSR, on cognitive performance, beta-amyloid (Aβ) peptides, and its feed-forward regulators regarding AD pathogenesis. METHODS: Sixteen nine-month-old C57BL/6 male mice were equally divided into the CSR and control groups. CSR was achieved by application of a slowly rotating drum for 2 months. The Morris water maze test was used to assess cognitive impairment...
March 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28132781/inhibitory-effect-of-punicalagin-on-lipopolysaccharide-induced-neuroinflammation-oxidative-stress-and-memory-impairment-via-inhibition-of-nuclear-factor-kappab
#10
Young Eun Kim, Chul Ju Hwang, Hee Pom Lee, Chun Sik Kim, Dong Ju Son, Young Wan Ham, Mats Hellström, Sang-Bae Han, Hee Sik Kim, Eun Kyung Park, Jin Tae Hong
Neuroinflammation is significant in the pathogenesis and development of Alzheimer's disease (AD). Previously, we showed lipopolysaccharide (LPS)-induced neuroinflammation caused memory impairment. We investigated the possible preventive effects of punicalagin (PUN), a component of pomegranate, on memory deficiency caused by LPS, along with the fundamental mechanisms. LPS-treated cultured astrocytes and microglial BV-2 cells were investigated for anti-neuroinflammatory effects of PUN. PUN (1.5 mg/kg) ameliorates LPS (250 μg/kg daily 7 times)-induced memory impairment as well as prevents the LPS-induced expression of inflammatory proteins...
January 26, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28130638/marginal-vitamin-a-deficiency-facilitates-alzheimer-s-pathogenesis
#11
Jiaying Zeng, Li Chen, Zhe Wang, Qian Chen, Zhen Fan, Hongpeng Jiang, Yili Wu, Lan Ren, Jie Chen, Tingyu Li, Weihong Song
Deposition of amyloid β protein (Aβ) to form neuritic plaques in the brain is the unique pathological hallmark of Alzheimer's disease (AD). Aβ is derived from amyloid β precursor protein (APP) by β- and γ-secretase cleavages and turned over by glia in the central nervous system (CNS). Vitamin A deficiency (VAD) has been shown to affect cognitive functions. Marginal vitamin A deficiency (MVAD) is a serious and widespread public health problem among pregnant women and children in developing countries. However, the role of MVAD in the pathogenesis of AD remains elusive...
January 27, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28129943/beta-site-amyloid-precursor-protein-cleaving-enzyme-1-inhibition-impairs-synaptic-plasticity-via-seizure-protein-6
#12
Kaichuan Zhu, Xianyuan Xiang, Severin Filser, Petar Marinković, Mario M Dorostkar, Sophie Crux, Ulf Neumann, Derya R Shimshek, Gerhard Rammes, Christian Haass, Stefan F Lichtenthaler, Jenny M Gunnersen, Jochen Herms
BACKGROUND: Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a promising drug target for the treatment of Alzheimer's disease. Prolonged BACE1 inhibition interferes with structural and functional synaptic plasticity in mice, most likely by altering the metabolism of BACE1 substrates. Seizure protein 6 (SEZ6) is predominantly cleaved by BACE1, and Sez6 knockout mice share some phenotypes with BACE1 inhibitor-treated mice. We investigated whether SEZ6 is involved in BACE1 inhibition-induced structural and functional synaptic alterations...
December 26, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/28126681/nose-to-brain-delivery-of-bace1-sirna-loaded-in-solid-lipid-nanoparticles-for-alzheimer-s-therapy
#13
Giovanna Rassu, Elena Soddu, Anna Maria Posadino, Gianfranco Pintus, Bruno Sarmento, Paolo Giunchedi, Elisabetta Gavini
We designed a delivery system to obtain an efficient and optimal nose-to-brain transport of BACE1 siRNA, potentially useful in the treatment of Alzheimer's disease. We selected a cell-penetrating peptide, the short peptide derived from rabies virus glycoprotein known as RVG-9R, to increase the transcellular pathway in neuronal cells. The optimal molar ratio between RVG-9R and BACE1 siRNA was elucidated. The complex between the two was then encapsulated. We propose chitosan-coated and uncoated solid lipid nanoparticles (SLNs) as a nasal delivery system capable of exploiting both olfactory and trigeminal nerve pathways...
January 19, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28124585/poor-safety-and-tolerability-hamper-reaching-a-potentially-therapeutic-dose-in-the-use-of-thalidomide-for-alzheimer-s-disease-results-from-a-double-blind-placebo-controlled-trial
#14
Boris Decourt, Denise Drumm-Gurnee, Jeffrey Wilson, Sandra Jacobson, Christine Belden, Sherye Sirrel, Michael Ahmadi, Holly Shill, Jessica Powell, Aaron Walker, Amanda Gonzales, Mimi Macias, Marwan N Sabbagh
INTRODUCTION: To date there is no cure for Alzheimer's disease (AD). After amyloid beta immunotherapies have failed to meet primary endpoints of slowing cognitive decline in AD subjects, the inhibition of the beta-secretase BACE1 appears as a promising therapeutic approach. Pre-clinical data obtained in APP23 mice suggested that the anti-cancer drug thalidomide decreases brainBACE1 and A levels. This prompted us to develop an NIH-supported Phase IIa clinical trial to test the potential of thalidomide for AD...
January 17, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28109317/sorting-nexin-4-regulates-%C3%AE-amyloid-production-by-modulating-%C3%AE-site-activating-cleavage-enzyme-1
#15
Na-Young Kim, Mi-Hyang Cho, Se-Hoon Won, Hoe-Jin Kang, Seung-Yong Yoon, Dong-Hou Kim
BACKGROUND: Amyloid precursor protein (APP) is cleaved by β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) to produce β-amyloid (Aβ), a critical pathogenic peptide in Alzheimer's disease (AD). Aβ generation can be affected by the intracellular trafficking of APP or its related secretases, which is thus important to understanding its pathological alterations. Although sorting nexin (SNX) family proteins regulate this trafficking, the relevance and role of sorting nexin-4 (SNX4) regarding AD has not been studied yet...
January 21, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28107420/the-polyherbal-wattana-formula-displays-anti-amyloidogenic-properties-by-increasing-%C3%AE-secretase-activities
#16
Htut Htut Htoo, Suveerawan Limsuvan, Onusa Thamsermsang, Jean-François Hernandez, Frédéric Checler, Piyarat Govitrapong, Narawut Pakaprot, Pravit Akarasereenont, Bruno Vincent
Alzheimer's disease is characterized by the deposition of insoluble amyloid-β peptides produced from the β-amyloid precursor protein (βAPP). Because α-secretase cleavage by ADAM10 and ADAM17 takes place in the middle of Aβ, its activation is considered as a promising anti-AD therapeutic track. Here we establish that the polyherbal Wattana formula (WNF) stimulates sAPPα production in cells of neuronal and non-neuronal origins through an increase of both ADAM10 and ADAM17 catalytic activities with no modification of BACE1 activity and expression...
2017: PloS One
https://www.readbyqxmd.com/read/28103438/acylguanidine-beta-secretase-1-inhibitors-a-combined-experimental-and-free-energy-perturbation-study
#17
Henrik Keränen, Laura Pérez-Benito, Myriam Ciordia, Francisca Delgado, Thomas B Steinbrecher, Daniel Oehlrich, Herman W T van Vlijmen, Andrés A Trabanco, Gary Tresadern
A series of acylguanidine beta secretase 1 (BACE1) inhibitors with modified scaffold and P3 pocket substituent was synthesized and studied with free energy perturbation (FEP) calculations. The resulting molecules showed potencies in enzymatic BACE1 inhibition assays up to 1 nM. The correlation between the predicted activity from the FEP calculations and the experimental activity was good for the P3 pocket substituents. The average mean unsigned error (MUE) between prediction and experiment was 0.68 ± 0.17 kcal/mol for the default 5 ns lambda window simulation time improving to 0...
February 3, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28099462/acute-and-chronic-sustained-hypoxia-do-not-substantially-regulate-amyloid-%C3%AE-peptide-generation-in-vivo
#18
Alberto Serrano-Pozo, Manuel A Sánchez-García, Antonio Heras-Garvín, Rosana March-Díaz, Victoria Navarro, Marisa Vizuete, José López-Barneo, Javier Vitorica, Alberto Pascual
BACKGROUND: Recent epidemiological evidence has linked hypoxia with the development of Alzheimer disease (AD). A number of in vitro and in vivo studies have reported that hypoxia can induce amyloid-β peptide accumulation through various molecular mechanisms including the up-regulation of the amyloid-β precursor protein, the β-secretase Bace1, or the γγ-secretase complex components, as well as the down-regulation of Aβ-degrading enzymes. OBJECTIVES: To investigate the effects of acute and chronic sustained hypoxia in Aβ generation in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28093699/anti-alzheimer-s-disease-activity-of-compounds-from-the-root-bark-of-morus-alba-l
#19
Eun Bi Kuk, A Ra Jo, Seo In Oh, Hee Sook Sohn, Su Hui Seong, Anupom Roy, Jae Sue Choi, Hyun Ah Jung
The inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) plays important roles in prevention and treatment of Alzheimer's disease (AD). Among the individual parts of Morus alba L. including root bark, branches, leaves, and fruits, the root bark showed the most potent enzyme inhibitory activities. Therefore, the aim of this study was to evaluate the anti-AD activity of the M. alba root bark and its isolate compounds, including mulberrofuran G (1), albanol B (2), and kuwanon G (3) via inhibition of AChE, BChE, and BACE1...
January 16, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28093254/risperidone-ameliorated-a%C3%AE-1-42-induced-cognitive-and-hippocampal-synaptic-impairments-in-mice
#20
Lingzhi Wu, Xiaowen Feng, Tingting Li, Baojuan Sun, Muhammad Zahid Khan, Ling He
Alzheimer's disease (AD) is a complex neurodegenerative disorder with cognitive impairment and major neuropathologic hallmark of amyloid-beta (Aβ) peptides. Risperidone, an atypical antipsychotic, can improve concentration and cognitive deficit in schizophrenia patients. In this study, behavior tests including Morris Water Maze test, Step-through passive avoidance test, Open Field test, Step-Down test, Hole-Board test and Novel object recognition test were preformed to examine the effect of Risperidone on Aβ1-42-induced cognitive dysfunction in both long-term and short-term memory...
March 30, 2017: Behavioural Brain Research
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