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https://www.readbyqxmd.com/read/27914299/the-effects-of-fluorine-substitution-on-the-chemical-properties-and-inhibitory-capacity-of-donepezil-anti-alzheimer-drug-density-functional-theory-and-molecular-docking-calculations
#1
Azita Khosravan, Safora Marani, Mohammad Sadegh Sadeghi Googheri
Drug fluorination has the potential to reproduce useful drugs with decreasing the side effect of them. Identifying the effect of this improvement on the chemical properties and biological interactions of drug symbolizes a meaningful progress in drug design. Here the fluorination of Donepezil as an anti-Alzheimer drug, including 7 fluorinated derivatives of it, was investigated computationally. In the first part of our calculations, the most important chemical properties of drug that affects the drug efficiency were investigated by applying the M06/6-31g (d, p) and M062X/6-31g (d, p) levels of theories...
November 25, 2016: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/27914038/serotonin-5-ht6-receptor-antagonists-in-alzheimer-s-disease-therapeutic-rationale-and-current-development-status
#2
Hilda Ferrero, Maite Solas, Paul T Francis, Maria J Ramirez
Alzheimer's disease (AD) is the most common cause of dementia in elderly people. Because of the lack of effective treatments for this illness, research focused on identifying compounds that restore cognition and functional impairments in patients with AD is a very active field. Since its discovery in 1993, the serotonin 5-HT6 receptor has received increasing attention, and a growing number of studies supported 5-HT6 receptor antagonism as a target for improving cognitive dysfunction in AD. This article reviews the rationale behind investigations into the targeting of 5-HT6 receptors as a symptomatic treatment for cognitive and/or behavioral symptoms of AD...
December 3, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27913965/plasma-amyloid-beta-levels-in-patients-with-different-types-of-cancer
#3
Wang-Sheng Jin, Xian-Le Bu, Yu-Hui Liu, Lin-Lin Shen, Zhen-Qian Zhuang, Shu-Sheng Jiao, Chi Zhu, Qing-Hua Wang, Hua-Dong Zhou, Tao Zhang, Yan-Jiang Wang
Several epidemiological investigations indicate that cancer survivors have a lower risk for Alzheimer's disease (AD) and vice versa. However, the associations between plasma amyloid-beta (Aβ) levels with cancer remain largely unknown. In this case-control study, 110 cancer patients, 70 AD patients, and 70 age- and gender-matched normal controls were recruited. The cancer types include esophagus cancer, colorectal cancer, hepatic cancer, and lung cancer, all of which were reported to be associated with a lower risk for AD...
December 3, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27913964/intracerebroventricular-streptozotocin-as-a-model-of-alzheimer-s-disease-neurochemical-and-behavioral-characterization-in-mice
#4
Katherine Garcia Ravelli, Barbara Dos Anjos Rosário, Rosana Camarini, Marina Sorrentino Hernandes, Luiz Roberto Britto
Streptozotocin has been widely used to mimic some aspects of Alzheimer's disease (AD). However, especially in mice, several characteristics involved in the streptozotocin (STZ)-induced AD pathology are not well known. The main purpose of this study was to evaluate temporally the expression of AD-related proteins, such as amyloid-β (Aβ), choline acetyltransferase (ChAT), synapsin, axonal neurofilaments, and phosphorylated Tau in the hippocampus following intracerebroventricular (icv) administration of STZ in adult mice...
December 2, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27913963/erratum-to-altered-nr4a-subfamily-gene-expression-level-in-peripheral-blood-of-parkinson-s-and-alzheimer-s-disease-patients
#5
Francesca Montarolo, Simona Perga, Serena Martire, De'sire'e Nicole Navone, Alberto Marchet, Daniela Leotta, Antonio Bertolotto
No abstract text is available yet for this article.
December 2, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27913818/-amyloid-positron-emission-tomography-with-18-%C3%A2-f-florbetaben-in-the-diagnostic-workup-of-dementia-patients
#6
S Schönecker, C Prix, T Raiser, N Ackl, E Wlasich, G Stenglein-Krapf, E Mille, M Brendel, O Sabri, M Patt, H Barthel, P Bartenstein, J Levin, A Rominger, A Danek
BACKGROUND: To this day the definite diagnosis of Alzheimer's disease still relies on post-mortem histopathological detection of neurofibrillary tangles and beta-amyloid deposits. Amyloid positron emission tomography (PET) is a new diagnostic tool that enables the in vivo quantification of pathological beta-amyloid deposits. The aim of the current study was to evaluate to what extent (18)F-florbetaben-PET (FBB-PET) influences the diagnosis of patients with dementia. MATERIAL AND METHODS: Imaging with FBB-PET was performed on 33 patients from our outpatient department for cognitive neurology...
December 2, 2016: Der Nervenarzt
https://www.readbyqxmd.com/read/27913407/whole-brain-analysis-reveals-increased-neuroanatomical-asymmetries-in-dementia-for-hippocampus-and-amygdala
#7
Christian Wachinger, David H Salat, Michael Weiner, Martin Reuter
Structural magnetic resonance imaging data are frequently analysed to reveal morphological changes of the human brain in dementia. Most contemporary imaging biomarkers are scalar values, such as the volume of a structure, and may miss the localized morphological variation of early presymptomatic disease progression. Neuroanatomical shape descriptors, however, can represent complex geometric information of individual anatomical regions and may demonstrate increased sensitivity in association studies. Yet, they remain largely unexplored...
December 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27913295/dissection-of-functional-lncrnas-in-alzheimer-s-disease-by-construction-and-analysis-of-lncrna-mrna-networks-based-on-competitive-endogenous-rnas
#8
Lian-Kun Wang, Xiao-Feng Chen, Dan-Dan He, You Li, Jin Fu
Alzheimer's disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly, and intracellular neurofibrillary tangles (NFTs) are one of the pathological features of AD. Recent studies have suggested long noncoding RNAs (lncRNAs) play important roles in AD. Competing endogenous RNAs (ceRNAs) is a mechanism that has recently been proposed, in which lncRNAs compete for common miRNA-binding sites with mRNAs. However, the roles of lncRNAs and ceRNA in AD NFTs is limited. In this study, we constructed a global triple network based on ceRNA theory, then an AD NFT lncRNA-mRNA network (NFTLMN) was generated...
November 29, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27913252/sex-and-gender-differences-in-the-treatment-of-alzheimer-s-disease-a-systematic-review-of-randomized-controlled-trials
#9
Marco Canevelli, Federica Quarata, Francesca Remiddi, Flaminia Lucchini, Eleonora Lacorte, Nicola Vanacore, Giuseppe Bruno, Matteo Cesari
In recent years, epidemiological, clinical, and biological evidence has drawn the attention on the influence of sex and gender on Alzheimer's disease (AD). Nevertheless, not enough attention has been paid to their impact on treatment outcomes. The present study is aimed at systematically retrieve, review and discuss data coming from available randomized placebo-controlled trials (RCTs) on currently marketed treatments for AD (i.e., cholinesterase inhibitors [ChEIs] and memantine) in order to describe possible sex and gender differences in their efficacy, safety and tolerability...
November 29, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27913125/apomorphine-therapy-in-parkinson-s-and-future-directions
#10
Nataliya Titova, K Ray Chaudhuri
Apomorphine infusion or injection is an important dopamine agonist non-oral therapy usually used in advanced Parkinson's disease (PD) with refractory motor fluctuations. The drug also has appreciable efficacy for nonmotor fluctuations and is the quickest to reverse predictable "off" periods. Current subcutaneous administration, however, is complicated by problems associated with needle-based therapies, such as skin nodule formation, skin irritation, and avoidance of this treatment option by needle-phobic subjects...
November 30, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/27912740/effectiveness-and-cost-effectiveness-of-an-in-home-respite-care-program-in-supporting-informal-caregivers-of-people-with-dementia-design-of-a-comparative-study
#11
Sophie Vandepitte, Nele Van Den Noortgate, Koen Putman, Sofie Verhaeghe, Lieven Annemans
BACKGROUND: Frequent hospitalization and permanent nursing home placement not only affect the well-being of persons with dementia, but also place great financial strain on society. Therefore, it is important to create effective strategies to support informal caregivers so that they can continue to perform their demanding role. Preliminary qualitative evidence suggests that community-based respite services can actually be important for caregivers, and that the level of evidence should be further established in terms of effectiveness...
December 2, 2016: BMC Geriatrics
https://www.readbyqxmd.com/read/27911827/tau-prions-from-alzheimer-s-disease-and-chronic-traumatic-encephalopathy-patients-propagate-in-cultured-cells
#12
Amanda L Woerman, Atsushi Aoyagi, Smita Patel, Sabeen A Kazmi, Iryna Lobach, Lea T Grinberg, Ann C McKee, William W Seeley, Steven H Olson, Stanley B Prusiner
Tau prions are thought to aggregate in the central nervous system, resulting in neurodegeneration. Among the tauopathies, Alzheimer's disease (AD) is the most common, whereas argyrophilic grain disease (AGD), corticobasal degeneration (CBD), chronic traumatic encephalopathy (CTE), Pick's disease (PiD), and progressive supranuclear palsy (PSP) are less prevalent. Brain extracts from deceased individuals with PiD, a neurodegenerative disorder characterized by three-repeat (3R) tau prions, were used to infect HEK293T cells expressing 3R tau fused to yellow fluorescent protein (YFP)...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911757/local-and-use-dependent-effects-of-%C3%AE-amyloid-oligomers-on-nmda-receptor-function-revealed-by-optical-quantal-analysis
#13
Brooke L Sinnen, Aaron B Bowen, Emily S Gibson, Matthew J Kennedy
: Beta amyloid (Aβ) triggers the elimination of excitatory synaptic connections in the CNS, an early manifestation of Alzheimer's disease. Oligomeric assemblies of Aβ peptide associate with excitatory synapses resulting in synapse elimination through a process that requires NMDA-type glutamate receptor activation. Whether Aβ affects synaptic NMDA receptor (NMDAR) function directly and acts locally at synapses to which it has bound and whether synaptic activity influences Aβ synaptic binding and synaptotoxicity have remained fundamental questions...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27911749/casting-a-wide-net-role-of-perineuronal-nets-in-neural-plasticity
#14
Barbara A Sorg, Sabina Berretta, Jordan M Blacktop, James W Fawcett, Hiroshi Kitagawa, Jessica C F Kwok, Marta Miquel
Perineuronal nets (PNNs) are unique extracellular matrix structures that wrap around certain neurons in the CNS during development and control plasticity in the adult CNS. They appear to contribute to a wide range of diseases/disorders of the brain, are involved in recovery from spinal cord injury, and are altered during aging, learning and memory, and after exposure to drugs of abuse. Here the focus is on how a major component of PNNs, chondroitin sulfate proteoglycans, control plasticity, and on the role of PNNs in memory in normal aging, in a tauopathy model of Alzheimer's disease, and in drug addiction...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27911736/the-multiple-assemblies-of-vdac-from-conformational-heterogeneity-to-%C3%AE-aggregation-and-amyloid-formation
#15
REVIEW
Alexandre Boulbrima, Davina Temple, Georgios Psakis
From their cellular localisation, to their atomic structure and their involvement in mitochondrial-driven cell death, voltage-dependent anion channels (VDACs) have challenged the scientific community with enigmas and paradoxes for over four decades. VDACs form active monomer channels in lipid bilayers, but they can also organise in multimeric assemblies. What induces, regulates and/or controls the monomer-multimer dynamics at the cellular level is not known. However, these state transitions appear to be relevant for mitochondria in making life or death decisions and for driving developmental processes...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911442/palmitoylation-of-caspase-6-by-hip14-regulates-its-activation
#16
Niels H Skotte, Shaun S Sanders, Roshni R Singaraja, Dagmar E Ehrnhoefer, Kuljeet Vaid, Xiaofan Qiu, Srinivasaragavan Kannan, Chandra Verma, Michael R Hayden
Caspase-6 (CASP6) has an important role in axonal degeneration during neuronal apoptosis and in the neurodegenerative diseases Alzheimer and Huntington disease. Decreasing CASP6 activity may help to restore neuronal function in these and other diseases such as stroke and ischemia, where increased CASP6 activity has been implicated. The key to finding approaches to decrease CASP6 activity is a deeper understanding of the mechanisms regulating CASP6 activation. We show that CASP6 is posttranslationally palmitoylated by the palmitoyl acyltransferase HIP14 and that the palmitoylation of CASP6 inhibits its activation...
December 2, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27911416/the-indirect-neuron-astrocyte-coculture-assay-an-in-vitro-set-up-for-the-detailed-investigation-of-neuron-glia-interactions
#17
Christine Gottschling, Egor Dzyubenko, Maren Geissler, Andreas Faissner
Proper neuronal development and function is the prerequisite of the developing and the adult brain. However, the mechanisms underlying the highly controlled formation and maintenance of complex neuronal networks are not completely understood thus far. The open questions concerning neurons in health and disease are diverse and reaching from understanding the basic development to investigating human related pathologies, e.g., Alzheimer's disease and Schizophrenia. The most detailed analysis of neurons can be performed in vitro...
November 14, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911329/comparison-of-model-based-indices-of%C3%A2-cerebral-autoregulation-and-vasomotor-reactivity-using-transcranial-doppler-versus-near-infrared-spectroscopy-in%C3%A2-patients-with-amnestic-mild-cognitive-impairment
#18
Vasilis Z Marmarelis, Dae C Shin, Takashi Tarumi, Rong Zhang
We recently introduced model-based "physiomarkers" of dynamic cerebral autoregulation and CO2 vasomotor reactivity as an aid for diagnosis of early-stage Alzheimer's disease (AD) [1], where significant impairment of dynamic vasomotor reactivity (DVR) was observed in early-stage AD patients relative to age-matched controls. Milder impairment of DVR was shown in patients with amnestic mild cognitive impairment (MCI) using the same approach in a subsequent study [2]. The advocated approach utilizes subject-specific data-based models of cerebral hemodynamics to quantify the dynamic effects of resting-state changes in arterial blood pressure and end-tidal CO2 (the putative inputs) upon cerebral blood flow velocity (the putative output) measured at the middle cerebral artery via transcranial Doppler (TCD)...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911328/the-clinical-use-of-cerebrospinal-fluid-biomarkers-for-alzheimer-s-disease-diagnosis-the-italian-selfie
#19
Giulia M Sancesario, Sofia Toniolo, Davide Chiasserini, Simona G Di Santo, Josh Zegeer, Gaetano Bernardi, Massimo Musicco, Carlo Caltagirone, Lucilla Parnetti, Sergio Bernardini
Although the use of cerebrospinal fluid (CSF) amyloid β1-42 (Aβ42), tau (T-tau), and phosphorylated tau (p-tau181) gives added diagnostic and prognostic values, the diffusion is still limited in clinical practice and only a restricted number of patients receive an integrated clinico-biological diagnosis. By a survey, we aimed to do a "selfie" of the use and diffusion of CSF biomarkers of dementia in Italy, the standardization of pre-analytical procedures, the harmonization of ranges, and the participation to Quality Control programs...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911327/anticholinergic-exposure-and-risk-of-pneumonia-in-persons-with-alzheimer-s-disease-a-nested-case-control-study
#20
Pasi Lampela, Anna-Maija Tolppanen, Antti Tanskanen, Jari Tiihonen, Sirpa Hartikainen, Heidi Taipale
BACKGROUND: Risk of pneumonia is increased in persons with Alzheimer's disease (AD). In some studies, anticholinergic drugs (AC) have been associated with an increased pneumonia risk. OBJECTIVE: We analyzed the risk of pneumonia associated with ACs in persons with AD. METHODS: We performed a nested case-control study using register-based data from a Finnish nationwide MEDALZ cohort including all community-dwelling persons diagnosed with AD during 2005-2011...
November 28, 2016: Journal of Alzheimer's Disease: JAD
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