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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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Bin Liu, Junming Xia, Yali Chen, Jun Zhang
Neonatal exposure to volatile anesthetics causes apoptotic neurodegeneration in the developing brain, possibly leading to neurocognitive deficits in adulthood. Endoplasmic reticulum (ER) stress might be associated with sevoflurane (sevo)-induced neuroapoptosis. However, the signaling pathway regulating sevo-induced neuroapoptosis is not understood. We investigated the effects of neonatal sevo exposure on ER signaling pathway activation. Seven-day-old mouse pups were divided into control (C) and sevo (S; 3 % sevo exposure, 6 h) groups...
September 28, 2016: Neurotoxicity Research
Sonia Do Carmo, Cecilia E Hanzel, Marie L Jacobs, Ziv Machnes, M Florencia Iulita, Jingyun Yang, Lei Yu, Adriana Ducatenzeiler, Marc Danik, Lionel S Breuillaud, David A Bennett, Moshe Szyf, A Claudio Cuello
General DNA hypomethylation is associated with Alzheimer's disease (AD), but it is unclear when DNA hypomethylation starts or plays a role in AD pathology or whether DNA re-methylation would rescue early amyloid-related cognitive impairments. In an APP transgenic mouse model of AD-like amyloid pathology we found that early intraneuronal amyloid beta build-up is sufficient to unleash a global and beta-site amyloid precursor protein cleaving enzyme 1 (bace-1) DNA demethylation in AD-vulnerable brain regions. S-adenosylmethionine administration at these early stages abolished this hypomethylation, diminished the amyloid pathology and restored cognitive capabilities...
September 29, 2016: Scientific Reports
Francesco Panza, Davide Seripa, Vincenzo Solfrizzi, Bruno P Imbimbo, Madia Lozupone, Antonio Leo, Rodolfo Sardone, Gaetano Gagliardi, Lucia Lofano, Bianca C Creanza, Paola Bisceglia, Antonio Daniele, Antonello Bellomo, Antonio Greco, Giancarlo Logroscino
Currently available drugs against Alzheimer's disease (AD) target cholinergic and glutamatergic neurotransmissions without affecting the underlying disease process. Putative disease-modifying drugs are in development and target β-amyloid (Aβ) peptide and tau protein, the principal neurophatological hallmarks of the disease. Areas covered: Phase III clinical studies of emerging anti-Aβ drugs for the treatment of AD were searched in US and EU clinical trial registries and in the medical literature until May 2016...
October 6, 2016: Expert Opinion on Emerging Drugs
Christel M Middeldorp, Anke R Hammerschlag, Klaasjan G Ouwens, Maria M Groen-Blokhuis, Beate St Pourcain, Corina U Greven, Irene Pappa, Carla M T Tiesler, Wei Ang, Ilja M Nolte, Natalia Vilor-Tejedor, Jonas Bacelis, Jane L Ebejer, Huiying Zhao, Gareth E Davies, Erik A Ehli, David M Evans, Iryna O Fedko, Mònica Guxens, Jouke-Jan Hottenga, James J Hudziak, Astanand Jugessur, John P Kemp, Eva Krapohl, Nicholas G Martin, Mario Murcia, Ronny Myhre, Johan Ormel, Susan M Ring, Marie Standl, Evie Stergiakouli, Camilla Stoltenberg, Elisabeth Thiering, Nicholas J Timpson, Maciej Trzaskowski, Peter J van der Most, Carol Wang, Dale R Nyholt, Sarah E Medland, Benjamin Neale, Bo Jacobsson, Jordi Sunyer, Catharina A Hartman, Andrew J O Whitehouse, Craig E Pennell, Joachim Heinrich, Robert Plomin, George Davey Smith, Henning Tiemeier, Danielle Posthuma, Dorret I Boomsma
OBJECTIVE: The aims of this study were to elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. METHOD: Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (<13 years of age) from nine population-based cohorts...
October 2016: Journal of the American Academy of Child and Adolescent Psychiatry
Inci Kazkayasi, Muhammad-Al-Mustafa Ismail, Cristina Parrado-Fernandez, Ingemar Björkhem, Can Pekiner, Serdar Uma, Angel Cedazo-Minguez, Nihan Burul-Bozkurt
Several studies demonstrated that Diabetes mellitus (DM) enhances the risk for Alzheimer's disease (AD). Although hyperglycemia and perturbed function of insulin signaling have been proposed to contribute to AD pathogenesis, the molecular mechanisms behind this association is not clear yet. Seladin-1 is an enzyme catalyzing the last step in cholesterol biosynthesis converting desmosterol to cholesterol. The neuroprotective function of seladin-1 has gained interest in AD research recently. Seladin-1 has anti-apoptotic properties and regulates the expression of β-secretase (BACE-1)...
October 28, 2016: Neuroscience Letters
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