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https://www.readbyqxmd.com/read/27889467/treadmill-exercise-decreases-amyloid-%C3%AE-burden-possibly-via-activation-of-sirt-1-signaling-in-a-mouse-model-of-alzheimer-s-disease
#1
Jung-Hoon Koo, Eun-Bum Kang, Yoo-Sung Oh, Dae-Seung Yang, Joon-Yong Cho
Accumulation of amyloid-β (Aβ) correlates significantly with progressive cognitive deficits, a main symptom of Alzheimer's disease (AD). Although treadmill exercise reduces Aβ levels, the molecular mechanisms underlying the effects are not fully understood. We hypothesize that treadmill exercise decreases Aβ production and alleviates cognitive deficits by activating the non-amyloidogenic pathway via SIRT-1 signaling. Treadmill exercise improved cognitive deficits and alleviated neurotoxicity. Most importantly, treadmill exercise increased SIRT-1 level, which subsequently resulted in increased ADAM-10 level by down-regulation of ROCK-1 and upregulation of RARβ, ultimately facilitating the non-amyloidogenic pathway...
November 23, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27853315/a%C3%AE-42-oligomers-modulate-%C3%AE-secretase-through-an-xbp-1s-dependent-pathway-involving-hrd1
#2
Yannis Gerakis, Julie Dunys, Charlotte Bauer, Fréderic Checler
The aspartyl protease β-site APP cleaving enzyme, BACE1, is the rate-limiting enzyme involved in the production of amyloid-β peptide, which accumulates in both sporadic and familial cases of Alzheimer's disease and is at the center of gravity of the amyloid cascade hypothesis. In this context, unravelling the molecular mechanisms controlling BACE1 expression and activity in both physiological and pathological conditions remains of major importance. We previously demonstrated that Aβ controlled BACE1 transcription in an NFκB-dependent manner...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27821233/-effect-and-mechanism-of-traditional-chinese-herbs-against-a%C3%AE-expression-in-brain-tissues-of-mice-with-alzheimer-s-disease
#3
N N Zhou, R Zhu, X M Zhao, P Liang
Objective: To investigate the effects of gastrodin, astragaloside and paeoniflorin from three types of traditional Chinese herbs against on β-amyloid plaques and memory ability in 5XFAD Alzheimer's disease (AD) transgenic mice. Methods: Seventy 5XFAD mice were randomly divided into seven groups, namely gastrodin-high and gastrodin-low dose groups (GAS-H, GAS-L), astragaloside-high and astragaloside-low dose groups (AST-H, AST-L), and paeoniflorin-high and paeoniflorin-low dose groups (PAE-H, PAE-L), and positive control group...
November 8, 2016: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/27807285/the-bace1-inhibitor-verubecestat-mk-8931-reduces-cns-%C3%AE-amyloid-in-animal-models-and-in-alzheimer-s-disease-patients
#4
Matthew E Kennedy, Andrew W Stamford, Xia Chen, Kathleen Cox, Jared N Cumming, Marissa F Dockendorf, Michael Egan, Larry Ereshefsky, Robert A Hodgson, Lynn A Hyde, Stanford Jhee, Huub J Kleijn, Reshma Kuvelkar, Wei Li, Britta A Mattson, Hong Mei, John Palcza, Jack D Scott, Michael Tanen, Matthew D Troyer, Jack L Tseng, Julie A Stone, Eric M Parker, Mark S Forman
β-Amyloid (Aβ) peptides are thought to be critically involved in the etiology of Alzheimer's disease (AD). The aspartyl protease β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is required for the production of Aβ, and BACE1 inhibition is thus an attractive target for the treatment of AD. We show that verubecestat (MK-8931) is a potent, selective, structurally unique BACE1 inhibitor that reduced plasma, cerebrospinal fluid (CSF), and brain concentrations of Aβ40, Aβ42, and sAPPβ (a direct product of BACE1 enzymatic activity) after acute and chronic administration to rats and monkeys...
November 2, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27790089/proteomic-substrate-identification-for-membrane-proteases-in-the-brain
#5
REVIEW
Stephan A Müller, Simone D Scilabra, Stefan F Lichtenthaler
Cell-cell communication in the brain is controlled by multiple mechanisms, including proteolysis. Membrane-bound proteases generate signaling molecules from membrane-bound precursor proteins and control the length and function of cell surface membrane proteins. These proteases belong to different families, including members of the "a disintegrin and metalloprotease" (ADAM), the beta-site amyloid precursor protein cleaving enzymes (BACE), membrane-type matrix metalloproteases (MT-MMP) and rhomboids. Some of these proteases, in particular ADAM10 and BACE1 have been shown to be essential not only for the correct development of the mammalian brain, but also for myelination and maintaining neuronal connections in the adult nervous system...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27778760/effect-of-flavonoids-rich-extract-of-capparis-spinosa-on-inflammatory-involved-genes-in-amyloid-beta-peptide-injected-rat-model-of-alzheimer-s-disease
#6
Nazanin Mohebali, Seyed Abolhassan Shahzadeh Fazeli, Hossein Ghafoori, Zeinab Farahmand, Elham MohammadKhani, Faezeh Vakhshiteh, Abdolreza Ghamarian, Mansoureh Farhangniya, Mohammad Hossein Sanati
OBJECTIVES: Alzheimer's disease (AD) is one of the most common forms of neurodegenerative diseases. Despite vast ongoing researches focusing on the area, little is known about novel treatments. In this study, we aimed to survey the effects of Capparis spinosa (C. spinosa) extract on amyloid-beta peptide (Aβ)-injected rat. METHODS: For this purpose, hydroalcoholic extracts of caper leaf and fruit were prepared. Total phenolic content, DPPH, and FRAP assay were accomplished to determine antioxidant activity of C...
October 25, 2016: Nutritional Neuroscience
https://www.readbyqxmd.com/read/27777836/affinity-capturing-and-surface-enrichment-of-a-membrane-protein-embedded-in-a-continuous-supported-lipid-bilayer
#7
Anders Gunnarsson, Lisa Simonsson Nyström, Sabina Burazerovic, Jenny Gunnarsson, Arjan Snijder, Stefan Geschwindner, Fredrik Höök
Investigations of ligand-binding kinetics to membrane proteins are hampered by their poor stability and low expression levels, which often translates into sensitivity-related limitations impaired by low signal-to-noise ratios. Inspired by affinity capturing of water-soluble proteins, which utilizes water as the mobile phase, we demonstrate affinity capturing and local enrichment of membrane proteins by using a fluid lipid bilayer as the mobile phase. Specific membrane-protein capturing and enrichment in a microfluidic channel was accomplished by immobilizing a synthesized trivalent nitrilotriacetic acid (tris-NTA)-biotin conjugate...
October 2016: ChemistryOpen
https://www.readbyqxmd.com/read/27770745/computational-insights-into-the-protonation-states-of-catalytic-dyad-in-bace1-acyl-guanidine-based-inhibitor-complex
#8
Abdulkadir Kocak, Ismail Erol, Muslum Yildiz, Hatice Can
Developing small compound based drugs targeting the β-secretase (BACE) enzyme is one of the most promising strategies in treatment of the Alzheimer's disease. As the enzyme shows the activity based on the acid-base reaction at a very narrow pH range, the protonation state of aspartic acids with the residue number 32 and 228 (Asp32 and Asp228), which forms the active site dyad, along with the protonation state of the ligand (substrate or inhibitor) play very critical role in interactions between the ligand and enzyme...
October 17, 2016: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/27765347/neurohormetic-responses-of-quercetin-and-rutin-in-a-cell-line-over-expressing-the-amyloid-precursor-protein-appswe-cells
#9
Sagrario Martín-Aragón, Karim Lizeth Jiménez-Aliaga, Juana Benedí, Paloma Bermejo-Bescós
BACKGROUND: Plant secondary metabolites may induce adaptive cellular stress-responses in a variety of cells including neurons at the sub-toxic doses ingested by humans. Such 'neurohormesis' phenomenon, activated by flavonoids such as quercetin or rutin, may involve cell responses driven by modulation of signaling pathways which are responsible for its neuroprotective effects. PURPOSE: We attempt to explore the molecular mechanisms involved in the neurohormetic responses to quercetin and rutin exposure, in a SH-SY5Y cell line which stably overexpresses the amyloid precursor protein (APP) Swedish mutation, based on a biphasic concentration-response relationship for cell viability...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27750032/prevention-of-tau-increase-in-cerebrospinal-fluid-of-app-transgenic-mice-suggests-downstream-effect-of-bace1-inhibition
#10
Juliane Schelle, Lisa Häsler, Jens C Göpfert, Thomas O Joos, Hugo Vanderstichele, Erik Stoops, Ulf Neumann, Derya R Shimshek, Matthias Staufenbiel, Mathias Jucker, Stephan A Kaeser
INTRODUCTION: The inhibition of the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is a main therapeutic approach for the treatment of Alzheimer's disease (AD). We previously reported an age-related increase of tau protein in the cerebrospinal fluid (CSF) of Aβ precursor protein (APP) transgenic mice. METHODS: APP transgenic mice were treated with a potent BACE1 inhibitor. CSF tau and CSF Aβ levels were assessed. A novel high-sensitivity tau sandwich immunoassay was developed...
October 14, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27730514/intranasal-insulin-administration-ameliorates-streptozotocin-icv-induced-insulin-receptor-dysfunction-neuroinflammation-amyloidogenesis-and-memory-impairment-in-rats
#11
N Rajasekar, Chandishwar Nath, Kashif Hanif, Rakesh Shukla
Alzheimer's disease (AD) is associated with reduced insulin level and impairment of insulin receptor (IR) signaling in the brain, which correlates to amyloid pathology, neuroinflammation, and synaptic neurotoxicity. Clinical studies show that intranasal insulin improves memory in AD patients without peripheral hypoglycemia. However, neuroprotective molecular mechanism of the beneficial effect of intranasal insulin in AD pathology is unexplored. Therefore, we investigated the role of intranasal insulin on intracerebroventricular (ICV) streptozotocin (STZ)-induced memory impairment in rats as evaluated in the Morris water maze test...
October 11, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27716410/seizure-protein-6-and-its-homolog-seizure-6-like-protein-are-physiological-substrates-of-bace1-in-neurons
#12
Martina Pigoni, Johanna Wanngren, Peer-Hendrik Kuhn, Kathryn M Munro, Jenny M Gunnersen, Hiroshi Takeshima, Regina Feederle, Iryna Voytyuk, Bart De Strooper, Mikail D Levasseur, Brian J Hrupka, Stephan A Müller, Stefan F Lichtenthaler
BACKGROUND: The protease BACE1 (beta-site APP cleaving enzyme) is a major drug target in Alzheimer's disease. However, BACE1 therapeutic inhibition may cause unwanted adverse effects due to its additional functions in the nervous system, such as in myelination and neuronal connectivity. Additionally, recent proteomic studies investigating BACE1 inhibition in cell lines and cultured murine neurons identified a wider range of neuronal membrane proteins as potential BACE1 substrates, including seizure protein 6 (SEZ6) and its homolog SEZ6L...
October 5, 2016: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/27712576/multiple-targets-for-management-of-alzheimer-s-disease-a-review
#13
Sayeed Ahmad, Salman Akhtar, Qazi Mohammad Sajid Jamal, Syed Mohd Danish Rizvi, Mohammad A Kamal, M Kalim A Khan, Mohd Haris Siddiqui
AD is a progressive and irreversible neurodegenerative disease and the most common cause of dementia in the elderly population. Βeta- amyloid cascade formation along with several cytoskeleton abnormalities succeeding to the hyperphosphorylation of microtubule-associated tau protein in neurons leads to the elicitation of several neurotoxic incidents. As an outcome of these phenomena, steady growth of dementia in aged population is becoming ubiquitous in both developed and developing countries. Thus, the key aspiration is to endow with stable daily life functionality to the person suffering from dementia and to cut down or slower the symptoms of disease leading to disruptive behavior...
October 3, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27702637/aging-process-alters-hippocampal-and-cortical-secretase-activities-of-wistar-rats
#14
Karine Bertoldi, Laura Reck Cechinel, Bruna Schallenberger, Louisiana Meireles, Carla Basso, Gisele Agustini Lovatel, Lisiane Bernardi, Marcelo Lazzaron Lamers, Ionara Rodrigues Siqueira
A growing body of evidence has demonstrated amyloid plaques in aged brain; however, little attention has been given to amyloid precursor protein (APP) processing machinery during the healthy aging process. The amyloidogenic and non-amyloidogenic pathways, represented respectively by β- and α-secretases (BACE and TACE), are responsible for APP cleavage. Our working hypothesis is that the normal aging process could imbalance amyloidogenic and non-amyloidogenic pathways specifically BACE and TACE activities...
October 1, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27697060/prediction-of-anti-diabetic-drugs-as-dual-inhibitors-against-acetylcholinesterase-and-beta-secretase-a-neuroinformatics-study
#15
Sibhghatulla Shaikh, Syed Mohd Danish Rizvi, Tabinda Suhail, Shazi Shakil, Adel M Abuzenadah, Rukhsar Anis, Deeba Naaz, Mohd Haneef, Adnan Ahmad, Latafat Choudhary
An increasing number of research evidences indicate linkage between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD); the two most common diseases of aging. In addition, T2DM and AD also share some common pathophysiological features. Therefore, dual therapy that targets both the diseases can be regarded as a beneficial approach. Acetylcholinesterase (AChE) and beta-secretase (BACE) have been considered as potential therapeutic targets for AD. Accordingly, the piece of work presented here describes the binding of anti-diabetic drugs (Jardiance, Suiny and Nesina) with AChE and BACE so as to further investigate connecting bridges concerning the treatment of these two diseases...
October 3, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27697055/multitarget-tacrine-hybrids-with-neuroprotective-properties-to-confront-alzheimer-s-disease
#16
Katarina Spilovska, Jan Korabecny, Eugenie Nepovimova, Rafael Dolezal, Eva Mezeiova, Ondrej Soukup, Kamil Kuca
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder. Several hallmarks such as β-amyloid (Aβ) aggregation underlying amyloid plaque formation, τ-hyperphosphorylation leading to the production of neurofibrillary tangles, and decline in the number of cholinergic neurons appear to be fundamental in the pathophysiology of the disease. Other evidence points also to the involvement of oxidative stress, biometal dyshomeostasis, inflammation, and cell cycle regulatory failure. Taking into account such premises, many attractive targets for the development of anti-AD drugs have emerged...
September 27, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27689393/computational-modeling-of-%C3%AE-secretase-1-bace-1-inhibitors-using-ligand-based-approaches
#17
Govindan Subramanian, Bharath Ramsundar, Vijay Pande, Rajiah Aldrin Denny
The binding affinities (IC50) reported for diverse structural and chemical classes of human β-secretase 1 (BACE-1) inhibitors in literature were modeled using multiple in silico ligand based modeling approaches and statistical techniques. The descriptor space encompasses simple binary molecular fingerprint, one- and two-dimensional constitutional, physicochemical, and topological descriptors, and sophisticated three-dimensional molecular fields that require appropriate structural alignments of varied chemical scaffolds in one universal chemical space...
October 10, 2016: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/27688518/identifying-barriers-to-mental-health-help-seeking-among-young-adults-in-the-uk-a-cross-sectional-survey
#18
Keziban Salaheddin, Barbara Mason
BACKGROUND: Despite the high prevalence and burden of mental health problems among young people, studies have suggested that they infrequently seek professional help. Understanding the barriers to help-seeking is an important step towards facilitating early access to mental health services and improving psychological wellbeing. AIM: To investigate why young adults may choose not to seek any support for an emotional or mental health difficulty. DESIGN AND SETTING: A cross-sectional online survey of young adults aged 18-25 from the general UK population...
October 2016: British Journal of General Practice: the Journal of the Royal College of General Practitioners
https://www.readbyqxmd.com/read/27683838/factors-associated-with-attitudes-and-beliefs-of-elders-with-acute-low-back-pain-data-from-the-study-back-complaints-in-the-elders-bace
#19
Luiza F Teixeira, Leani S M Pereira, Silvia L A Silva, João M D Dias, Rosângela C Dias
Background: The attitudes and beliefs that older people have about acute low back pain (LBP) may influence the coping mechanisms and the adoption of treatment strategies in this population. Objective: The aim of this study was to identify the factors associated with the attitudes and beliefs of elderly patients with acute low back pain using the Back Beliefs Questionnaire. Method: This is a cross-sectional study with a subsample of the study "Back Complaints in the Elders" (BACE), composed of 532 older Brazilians of both genders with acute LBP...
September 15, 2016: Brazilian Journal of Physical Therapy
https://www.readbyqxmd.com/read/27683833/risk-of-falls-in-brazilian-elders-with-and-without-low-back-pain-assessed-using-the-physiological-profile-assessment-bace-study
#20
Nayza M B Rosa, Bárbara Z Queiroz, Renata A Lopes, Natalia R Sampaio, Daniele S Pereira, Leani S M Pereira
Background: Low back pain (LBP) is a common musculoskeletal condition among elders and is associated with falls. However, the underlying biological risk factors for falling among elders with LBP has been poorly investigated. The Physiological Profile Assessment (PPA) is a validated fall-risk assessment tool that involves the direct assessment of sensorimotor abilities and may contribute to the understanding of risk factors for falls among elders with LBP. Objective: To assess fall risk using the PPA in elders with and without LBP...
September 15, 2016: Brazilian Journal of Physical Therapy
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