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https://www.readbyqxmd.com/read/28934619/distinct-brain-metabolic-patterns-separately-associated-with-cognition-motor-function-and-aging-in-parkinson-s-disease-dementia
#1
Ji Hyun Ko, Audrey Katako, Maram Aljuaid, Andrew L Goertzen, Andrew Borys, Douglas E Hobson, Seok Min Kim, Chong Sik Lee
We explored whether patients with Parkinson's disease dementia (PDD) show a distinct spatial metabolic pattern that characterizes cognitive deficits in addition to motor dysfunction. Eighteen patients with PDD underwent 3 separate positron emission tomography sessions with [(18)F]fluorodeoxyglucose (for glucose metabolism), fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (for dopamine transporter density) and Pittsburgh compound-B (for beta-amyloid load). We confirmed in PDD versus normal controls, overall hypometabolism in the posterior and prefrontal brain regions accompanied with hypermetabolism in subcortical structures and the cerebellar vermis...
August 31, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28933595/phosphoproteome-based-kinase-activity-profiling-reveals-the-critical-role-of-map2k2-and-plk1-in-neuronal-autophagy
#2
Lei-Lei Chen, Yong-Bo Wang, Ju-Xian Song, Wan-Kun Deng, Jia-Hong Lu, Li-Li Ma, Chuan-Bin Yang, Min Li, Yu Xue
Recent studies have demonstrated that dysregulation of macroautophagy/autophagy may play a central role in the pathogenesis of neurodegenerative disorders, and the induction of autophagy protects against the toxic insults of aggregate-prone proteins by enhancing their clearance. Thus, autophagy has become a promising therapeutic target against neurodegenerative diseases. In this study, quantitative phosphoproteomic profiling together with a computational analysis was performed to delineate the phosphorylation signalling networks regulated by 2 natural neuroprotective autophagy enhancers, corynoxine (Cory) and corynoxine B (Cory B)...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28932758/iterative-image-processing-for-early-diagnostic-of-beta-amyloid-plaque-deposition-in-pre-clinical-alzheimer-s-disease-studies
#3
Nikolai V Slavine, Padmakar V Kulkarni, Roderick W McColl
PURPOSE: To test and evaluate an efficient iterative image processing strategy to improve the quality of sub-optimal pre-clinical PET images. A novel iterative resolution subsets-based method to reduce noise and enhance resolution (RSEMD) has been demonstrated on examples of PET imaging studies of Alzheimer's disease (AD) plaques deposition in mice brains. MATERIALS AND METHODS: The RSEMD method was applied to imaging studies of non-invasive detection of beta-amyloid plaque in transgenic mouse models of AD...
August 2017: Journal of Applied Bioinformatics & Computational Biology
https://www.readbyqxmd.com/read/28932173/efficient-and-inexpensive-transient-expression-of-multispecific-multivalent-antibodies-in-expi293-cells
#4
Xiaotian T Fang, Dag Sehlin, Lars Lannfelt, Stina Syvänen, Greta Hultqvist
BACKGROUND: Immunotherapy is a very fast expanding field within drug discovery and, hence, rapid and inexpensive expression of antibodies would be extremely valuable. Antibodies are, however, difficult to express. Multifunctional antibodies with additional binding domains further complicate the expression. Only few protocols describe the production of tetravalent bispecific antibodies and all with limited expression levels.. METHODS: Here, we describe a protocol that can produce functional tetravalent, bispecific antibodies at around 22 mg protein/l to a low cost...
2017: Biological Procedures Online
https://www.readbyqxmd.com/read/28930532/neuroprotective-role-of-asiatic-acid-in-aluminium-chloride-induced-rat-model-of-alzheimer-s-disease
#5
Mashoque Ahmad Rather, Arokiasamy Justin Thenmozhi, Thamilarasan Manivasagam, Mathiyazahan Dhivya Bharathi, Musthafa Mohamed Essa, Gilles J Guillemin
Alzheimer's disease (AD) is the most common form of dementia, characterized by memory loss, cognitive impairment and personality disorders accompanied by diffuse structural abnormalities in the brain of elderly people. The current investigation explored the neuroprotective potential of asiatic acid (AA), a natural triterpene of Centella asiatica on aluminium chloride (AlCl3) induced rat model of AD. Oral administration of AlCl3 (100 mg/kg b.w.) for 42 days significantly elevated the levels of Al, activity of acetyl cholinesterase and expressions of amyloid precursor protein, amyloid beta1-42, beta and gamma secretases, glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, interleukins -1β, 6, 4, 2, tumor necrosis factor alpha, inducible nitric oxide synthase, nuclear factor- k beta and cyclooxygenase-2 in the hippocampus and cortex  compared to the control group...
January 1, 2018: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28930140/identification-of-phlogacantholide-c-as-a-novel-adam10-enhancer-from-traditional-chinese-medicinal-plants
#6
Myriam Meineck, Florian Schuck, Sara Abdelfatah, Thomas Efferth, Kristina Endres
Background: Alzheimer's disease is one of the most prevalent dementias in the elderly population with increasing numbers of patients. One pivotal hallmark of this disorder is the deposition of protein aggregates stemming from neurotoxic amyloid-beta peptides. Synthesis of those peptides has been efficiently prevented in AD model mice by activation of an enzyme called alpha-secretase. Therefore, drugs with the capability to increase the expression of this enzyme, named ADAM10, have been suggested as a valuable therapeutic medication...
December 5, 2016: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28927263/molecular-and-cellular-basis-of-neurodegeneration-in-alzheimer-s-disease
#7
Sangyun Jeong
The most common form of senile dementia is Alzheimer's disease (AD), which is characterized by the extracellular deposition of amyloid beta-peptide (Abeta) plaques and the intracellular formation of neurofibrillary tangles (NFTs) in the cerebral cortex. Tau abnormalities are commonly observed in many neurodegenerative diseases including AD, Parkinson's disease, and Pick's disease. Interestingly, tau-mediated formation of NFTs in AD brains shows better correlation with cognitive impairment than Abeta plaque accumulation; pathological tau alone is sufficient to elicit frontotemporal dementia, but it does not cause AD...
September 20, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28926757/mn-ii-based-t1-and-t2-potential-mri-contrast-agent-appended-with-tryptamine-recognition-moiety-for-a%C3%AE-plaques
#8
Neeraj Rastogi, Nidhi Tyagi, Ovender Singh, B S Hemanth Kumar, Udai P Singh, Kaushik Ghosh, Raja Roy
We report the synthesis and characterization of manganese(II) complexes having pentadentate ligands L1 (2,6-bis(1-(2-phenyl-2-(pyridin-2-yl)hydrazono)ethyl)pyridine), L2 (methyl 2,6-bis((E)-1-(2-phenyl-2-(pyridin-2yl)hydrazono)ethyl)isonicotinate), L3 (N-(2-(1H-indol-3-yl)ethyl)-2,6-bis((E)-1-(2-phenyl-2-(pyridin2yl)hydrazono)ethyl)isonicotiamide) and their application as dual contrast agents for simultaneous T1 and T2 weighted magnetic resonance imaging. Single crystal analysis of all the complexes [Mn(II)L1, Mn(II)L2 and Mn(II)L3] confirm the formation of novel seven-coordinate manganese complexes with an inner sphere water and perchlorate ion...
September 5, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28919420/cationization-increases-brain-distribution-of-an-amyloid-beta-protofibril-selective-f-ab-2-fragment
#9
Stina Syvänen, Desirée Edén, Dag Sehlin
Antibodies and fragments thereof are, because of high selectivity for their targets, considered as potential therapeutics and biomarkers for several neurological disorders. However, due to their large molecular size, antibodies/fragments do not easily penetrate into the brain. The aim of the present study was to improve the brain distribution via adsorptive-mediated transcytosis of an amyloid-beta (Aβ) protofibril selective F(ab')2 fragment (F(ab')2-h158). F(ab')2-h158 was cationized to different extents and the specific and unspecific binding was studied in vitro...
September 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28919253/the-influence-of-acidic-media-on-the-effect-of-beta-amyloid-peptide-on-the-function-of-glycine-receptor-in-hippocampal-neurons
#10
J V Bukanova, E I Solntseva, R V Kondratenko, V G Skrebitsky
We have previously shown that application of beta-amyloid peptide 1-42 (Aβ) at picomolar/nanomolar concentrations caused a decrease in the peak amplitude and acceleration of desensitization of the glycine-activated chloride current (IGly) in hippocampal pyramidal neurons (Bukanova et al., 2016). The aim of this work was to study the effect of Aβ on IGly in an acidified medium. The relevance of this work is determined by the fact that the pathogenic effects of Aβ in Alzheimer's disease are usually accompanied by inflammatory processes and acidosis...
September 15, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28918420/computer-analysis-of-glioma-transcriptome-profiling-alternative-splicing-events
#11
Vladimir N Babenko, Natalya V Gubanova, Anatoly O Bragin, Irina V Chadaeva, Gennady V Vasiliev, Irina V Medvedeva, Alexey S Gaytan, Alexey L Krivoshapkin, Yuriy L Orlov
Here we present the analysis of alternative splicing events on an example of glioblastoma cell culture samples using a set of computer tools in combination with database integration. The gene expression profiles of glioblastoma were obtained from cell culture samples of primary glioblastoma which were isolated and processed for RNA extraction. Transcriptome profiling of normal brain samples and glioblastoma were done by Illumina sequencing. The significant differentially expressed exon-level probes and their corresponding genes were identified using a combination of the splicing index method...
September 18, 2017: Journal of Integrative Bioinformatics
https://www.readbyqxmd.com/read/28914134/blunted-cerebrovascular-response-is-associated-with-elevated-beta-amyloid
#12
Jason-Flor V Sisante, Eric D Vidoni, Kiersten Kirkendoll, Jaimie Ward, Yumei Liu, Sarah Kwapiszeski, Rebecca Maletsky, Jeffrey M Burns, Sandra A Billinger
The goal of this study was to explore the association of beta-amyloid accumulation and cerebrovascular response (CVR) in cognitively normal older adults. Beta-amyloid accumulation was characterized with [18F] Florbetapir positron emission tomography scans. CVR was calculated as middle cerebral artery blood flow velocity change from rest to moderate intensity exercise. We found that individuals with elevated beta-amyloid aggregation had a blunted CVR ( n = 25, age 70.1 ± 4.8; 3.3 ± 3.7 cm/s) compared to non-elevated individuals ( n = 45, age 72...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28913897/studying-the-progression-of-amyloid-pathology-and-its-therapy-using-translational-longitudinal-model-of-accumulation-and-distribution-of-amyloid-beta
#13
Tatiana Karelina, O Demin, Oleg Demin, Sridhar Duvvuri, Timothy Nicholas
Long term effects of amyloid targeted therapy can be studied using a mechanistic translational model of Aβ distribution and aggregation calibrated on published data in mouse and human species. AD pathology is modelled utilizing age-dependent pathological evolution for rate constants and several variants of explicit functions for Aβ toxicity influencing cognitive outcomes (Adas-cog). Preventive Aβ targeted therapies were simulated to minimize the Aβ difference from healthy physiological levels. Therapeutic targeted simulations provided similar predictions for mouse and human...
September 15, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28913718/identify-a-shared-neural-circuit-linking-multiple-neuropsychiatric-symptoms-with-alzheimer-s-pathology
#14
Xixi Wang, Ping Ren, Mark Mapstone, Yeates Conwell, Anton P Porsteinsson, John J Foxe, Rajeev D S Raizada, Feng Lin
Neuropsychiatric symptoms (NPS) are common in Alzheimer's disease (AD)-associated neurodegeneration. However, NPS lack a consistent relationship with AD pathology. It is unknown whether any common neural circuits can link these clinically disparate while mechanistically similar features with AD pathology. Here, we explored the neural circuits of NPS in AD-associated neurodegeneration using multivariate pattern analysis (MVPA) of resting-state functional MRI data. Data from 98 subjects (70 amnestic mild cognitive impairment and 28 AD subjects) were obtained...
September 15, 2017: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/28912896/investigation-of-the-safety-of-focused-ultrasound-induced-blood-brain-barrier-opening-in-a-natural-canine-model-of-aging
#15
Meaghan Anne O'Reilly, Ryan Matthew Jones, Edward Barrett, Anthony Schwab, Elizabeth Head, Kullervo Hynynen
Rationale: Ultrasound-mediated opening of the Blood-Brain Barrier(BBB) has shown exciting potential for the treatment of Alzheimer's disease(AD). Studies in transgenic mouse models have shown that this approach can reduce plaque pathology and improve spatial memory. Before clinical translation can occur the safety of the method needs to be tested in a larger brain that allows lower frequencies be used to treat larger tissue volumes, simulating clinical situations. Here we investigate the safety of opening the BBB in half of the brain in a large aged animal model with naturally occurring amyloid deposits...
2017: Theranostics
https://www.readbyqxmd.com/read/28912710/key-aging-associated-alterations-in-primary-microglia-response-to-beta-amyloid-stimulation
#16
Cláudia Caldeira, Carolina Cunha, Ana R Vaz, Ana S Falcão, Andreia Barateiro, Elsa Seixas, Adelaide Fernandes, Dora Brites
Alzheimer's disease (AD) is characterized by a progressive cognitive decline and believed to be driven by the self-aggregation of amyloid-β (Aβ) peptide into oligomers and fibrils that accumulate as senile plaques. It is widely accepted that microglia-mediated inflammation is a significant contributor to disease pathogenesis; however, different microglia phenotypes were identified along AD progression and excessive Aβ production was shown to dysregulate cell function. As so, the contribution of microglia to AD pathogenesis remains to be elucidated...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28911966/fluoxetine-administration-during-adolescence-attenuates-cognitive-and-synaptic-deficits-in-adult-3%C3%A3-tgad-mice
#17
Dong-Sheng Sun, Li-Feng Gao, Li Jin, Hao Wu, Qun Wang, You Zhou, Shuhao Fan, Xia Jiang, Dan Ke, Hao Lei, Jian-Zhi Wang, Gong-Ping Liu
Fluoxetine (FLX) has broad neurobiological functions and neuroprotective effects; however, the preventive effects of FLX on cognitive impairments in Alzheimer's disease (AD) have not been reported. Here, we studied whether adolescent administration of fluoxetine can prevent memory deficits in AD transgenic mice that harbour PS1m146v, APPswe and TauP301L mutations (3 × TgAD). FLX was applied through peritoneal injection to the mice at postnatal day 35 (p35) for 15 consecutive days, and the effects of FLX were observed at 6-month...
September 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28910862/effects-of-newly-synthesized-recombinant-human-amyloid-%C3%AE-complexes-and-poly-amyloid-%C3%AE-fibers-on-cell-apoptosis-and-cognitive-decline
#18
Soojin Park, Jae-Won Huh, Taekil Eom, Naeun Na, Youngjeon Lee, Ju-Sung Kim, Sun-Uk Kim, Insop Shim, Sang-Rae Lee, Ekyune Kim
The main pathological hallmark of Alzheimer's disease is the deposition of amyloid-β peptide (Aβ) in the brain. Aβ has been widely used to mimic several aspects of Alzheimer's disease. However, several characteristics of amyloid-induced Alzheimer's disease pathology are not well established, especially in mice. The present study aimed to develop a new Alzheimer's disease model by investigating how amyloid beta can be effectively aggregated using prokaryotes and eukaryotes. To express the Aβ42 complex in HEK293 cells, we cloned the Aβ42 region repeatedly and incorporated the resulting construct into a eukaryotic expression vector...
September 15, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28910180/nrf2-mediated-ho-1-induction-and-antineuroinflammatory-activities-of-halleridone
#19
Ji Yeon Seo, Euisun Pyo, Junsoo Park, Jong-Sang Kim, Sang Hyun Sung, Won Keun Oh
Nuclear factor E2-related factor 2 (Nrf2) is the master regulator of antioxidant enzymes and is known to act on the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathway. Few studies have examined the bioactivity of halleridone. Herein, we investigated whether halleridone, which was isolated from the stems of the plant Cornus walteri, could regulate Nrf2-mediated heme oxygenase (HO)-1 expression and prevent intramicroglial inflammation induced by amyloid beta (Aβ)1-42 overexpression...
September 14, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28910085/cholesterol-changes-the-mechanism-of-a%C3%AE-peptide-binding-to-the-dmpc-bilayer
#20
Christopher Lockhart, Dmitri K Klimov
Using isobaric-isothermal all-atom replica-exchange molecular dynamics (REMD) simulations, we investigated the equilibrium binding of Abeta10-40 monomers to the zwitterionic dimyristoylphosphatidylcholine (DMPC) bilayer containing cholesterol. Our previous REMD simulations, which studied binding of the same peptide to the cholesterol-free DMPC bilayer, served as a control, against which we measured the impact of cholesterol. Our findings are as follows. First, addition of cholesterol to the DMPC bilayer partially expels the Abeta peptide from the hydrophobic core and promotes its binding to bilayer polar headgroups...
September 14, 2017: Journal of Chemical Information and Modeling
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