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APP transport

Animesh Alexander Raha, James W Henderson, Simon R W Stott, Romina Vuono, Simona Foscarin, Robert P Friedland, Shahid H Zaman, Ruma Raha-Chowdhury
Neuroinflammation and activation of innate immunity are early events in neurodegenerative diseases including Alzheimer's disease (AD). Recently, a rare mutation in the gene Triggering receptor expressed on myeloid cells 2 (TREM2) has been associated with a substantial increase in the risk of developing late onset AD. To uncover the molecular mechanisms underlying this association, we investigated the RNA and protein expression of TREM2 in APP/PS1 transgenic mice. Our findings suggest that TREM2 not only plays a critical role in inflammation, but is also involved in neuronal cell survival and in neurogenesis...
September 20, 2016: Journal of Alzheimer's Disease: JAD
D Pedretti, A Molinari, C Fallico, S Guzzi
A series of experimental tracer tests were performed to explore the implications of the change in the pressure status of a heterogeneous bimodal aquifer for scale-dependent dispersion and mass-transfer processes. The sandbox was filled with sands and gravel channels and patches to form an alluvial-like bimodal aquifer. We performed multiple injections of a conservative tracer from 26 different locations of the sandbox and interpreted the resulting depth-integrated breakthrough curves (BTCs) at the central pumping well to obtain a scale-dependent distribution of local and field-integrated apparent longitudinal dispersivity (respectively, αL(loc) and αL(app))...
September 9, 2016: Journal of Contaminant Hydrology
Mathew A Sherman, Michael LaCroix, Fatou Amar, Megan E Larson, Colleen Forster, Adriano Aguzzi, David A Bennett, Martin Ramsden, Sylvain E Lesné
UNLABELLED: Despite the demonstration that amyloid-β (Aβ) can trigger increased tau phosphorylation and neurofibrillary tangle (NFT) formation in vivo, the molecular link associating Aβ and tau pathologies remains ill defined. Here, we observed that exposure of cultured primary neurons to Aβ trimers isolated from brain tissue of subjects with Alzheimer's disease led to a specific conformational change of tau detected by the antibody Alz50. A similar association was supported by postmortem human brain analyses...
September 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Guoxing Lin, Shaokuan Zheng, Xinli Liao
Pulsed field gradient (PFG) NMR is a noninvasive tool to study anomalous diffusion, which exists widely in many systems such as in polymer or biological systems, in porous material, in single file structures and in fractal geometries. In a real system, the diffusion could be a restricted or a tortuous anomalous diffusion, rather than a free diffusion as the domains for fast and slow transport could coexist. Though there are signal attenuation expressions for free anomalous diffusion in literature, the signal attenuation formalisms for restricted anomalous diffusion is very limited, except for a restricted time-fractional diffusion within a plate reported recently...
August 31, 2016: Journal of Magnetic Resonance
Katharina Marie Höflich, Cordian Beyer, Tim Clarner, Christoph Schmitz, Stella Nyamoya, Markus Kipp, Tanja Hochstrasser
Axonal damage has been identified as a significant contributor to permanent clinical disability in multiple sclerosis. In the context of demyelinating disorders, this destructive event can be the result of inflammation, demyelination and/or the activation of innate defense cells such as microglia or monocytes. The relative contribution of each of these variables to acute axonal injury is, however, unknown. In the present study, we compared the extent of acute axonal damage in three different murine demyelination models using anti-amyloid precursor protein (APP) immunohistochemistry...
November 1, 2016: Brain Research
John N Hahladakis, Antonis Latsos, Evangelos Gidarakos
The present work focused on evaluating the electrokinetic (EK) treatment of real contaminated sediments with toxic metals and polycyclic aromatic hydrocarbons (PAHs), using a big laboratory EK cell, periodic voltage and recently tested non-ionic surfactants. The results indicated that the "day on-night off" application mode of voltage, in conjunction with the selected solubilising agents, favoured the overall EK process. Arsenic, nickel and chromium exhibited the highest removal percentages, obtaining 83%, 67% and 63%, respectively, while zinc and lead attained 54% and 41% at the maximum...
December 15, 2016: Journal of Hazardous Materials
Garrett R Mullins, James H Harrison, David E Bruns
BACKGROUND: Pneumatic tube systems (PTSs) are convenient methods of patient sample transport in medical centers, but excessive acceleration force and time/distance traveled in the PTS have been correlated with increased blood-sample hemolysis. We investigated the utility of smartphones for monitoring of PTS-related variables. METHODS: Smartphones were sent through the PTS from several hospital locations. Each smartphone used 2 apps as data-loggers to record force of acceleration vs time...
November 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Zhao-Lin Cai, Jia-Jia Zhang, Ming Chen, Jin-Zhao Wang, Peng Xiao, Li Yang, Cheng Long
Though amyloid precursor protein (APP) can potentially be cleaved to generate the pathological amyloid β peptide (Aβ), APP itself plays an important role in regulating neuronal activity. APP deficiency causes functional impairment in cholinergic synaptic transmission and cognitive performance. However, the mechanisms underlying altered cholinergic synaptic transmission in APP knock-out mice (APP(-/-)) are poorly understood. In this study, we conducted in vivo extracellular recording to investigate cholinergic compound action potentials (CAPs) of the superior cervical ganglion (SCG) in APP(-/-) and littermate wild-type (WT) mice...
November 2016: Neuropharmacology
Matthias Schweinlin, Angela Rossi, Nina Lodes, Christian Lotz, Stephan Hackenberg, Maria Steinke, Heike Walles, Florian Groeber
In vitro test systems gain increasing importance in preclinical studies to increase the predictivity and reduce animal testing. Of special interest herein are barrier tissues that guard into the human body. These barriers are formed by highly specialized tissues such as the skin, the airways, and the intestine. However, to recapitulate these tissues, researchers are currently restricted by a lack of suitable supporting scaffolds. In this study, we present biological scaffolds based on decellularized porcine gut segments that offer a natural environment for cell growth and differentiation...
August 22, 2016: Drug Delivery and Translational Research
Pasquale Picone, Silvia Vilasi, Fabio Librizzi, Marco Contardi, Domenico Nuzzo, Luca Caruana, Sara Baldassano, Antonella Amato, Flavia Mulè, Pier Luigi San Biagio, Daniela Giacomazza, Marta Di Carlo
The onset of Alzheimer disease (AD) is influenced by several risk factors comprising diabetes. Within this context, antidiabetic drugs, including metformin, are investigated for their effect on AD. We report that in the C57B6/J mice, metformin is delivered to the brain where activates AMP-activated kinase (AMPK), its molecular target. This drug affects the levels of β-secretase (BACE1) and β-amyloid precursor protein (APP), promoting processing and aggregation of β-amyloid (Aβ), mainly in the cortex region...
August 2016: Aging
Marlène Cassar, Doris Kretzschmar
The Amyloid precursor protein (APP) has mainly been investigated in connection with its role in Alzheimer's Disease (AD) due to its cleavage resulting in the production of the Aβ peptides that accumulate in the plaques characteristic for this disease. However, APP is an evolutionary conserved protein that is not only found in humans but also in many other species, including Drosophila, suggesting an important physiological function. Besides Aβ, several other fragments are produced by the cleavage of APP; large secreted fragments derived from the N-terminus and a small intracellular C-terminal fragment...
2016: Frontiers in Molecular Neuroscience
Jennifer A Smith, Barbara S Slusher, Krystyna M Wozniak, Mohamed H Farah, Gregoriy Smiyun, Leslie Wilson, Stuart Feinstein, Mary Ann Jordan
Peripheral neuropathy is a serious, dose-limiting side effect of cancer treatment with microtubule-targeting drugs. Symptoms present in a "stocking-glove" distribution, with longest nerves affected most acutely, suggesting a length-dependent component to the toxicity. Axonal transport of ATP-producing mitochondria along neuronal microtubules from cell body to synapse is crucial to neuronal function. We compared the effects of the drugs paclitaxel and ixabepilone that bind along the lengths of microtubules and the drugs eribulin and vincristine that bind at microtubule ends, on mitochondrial trafficking in cultured human neuronal SK-N-SH cells and on axonal transport in mouse sciatic nerves...
September 1, 2016: Cancer Research
Lin Zhang, Shou-Ying Du, Yang Lu, Chang Liu, Zhi-Hao Tian, Chang Yang, Hui-Chao Wu, Zhen Wang
Nasal administration is a high-potential delivery system, particularly because it can provide a pathway from the nose to the brain. The objective of this research is to characterize puerarin transport across a Calu-3 cell monolayer used as a model of the nasal mucosa and to evaluate the influence of puerarin in combination with paeoniflorin and menthol to explore the enhanced mechanism of the permeability at the cell level. The apparent permeability coefficients (P app) of puerarin bidirectional transport were both <1...
2016: Drug Design, Development and Therapy
Brian Spencer, Paula A Desplats, Cassia R Overk, Elvira Valera-Martin, Robert A Rissman, Chengbiao Wu, Michael Mante, Anthony Adame, Jazmin Florio, Edward Rockenstein, Eliezer Masliah
UNLABELLED: Alzheimer's disease (AD) is characterized by the progressive accumulation of amyloid β (Aβ) and microtubule associate protein tau, leading to the selective degeneration of neurons in the neocortex, limbic system, and nucleus basalis, among others. Recent studies have shown that α-synuclein (α-syn) also accumulates in the brains of patients with AD and interacts with Aβ and tau, forming toxic hetero-oligomers. Although the involvement of α-syn has been investigated extensively in Lewy body disease, less is known about the role of this synaptic protein in AD...
July 27, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Funmilola C Thomas, Andre M Santana, Mary Waterston, Hayley Haining, Peter David Eckersall
BACKGROUND: Samples for diagnostic procedures often require some form of pre-analytical preparation for preservation or safe handling during transportation prior to analysis in the laboratory. This is particularly important for milk samples which frequently need preservatives to retain milk composition as close to that found in freshly collected samples as possible. METHODS: Milk samples were treated by heating at 56 °C for 30 min or preserved by addition of either potassium dichromate or bronopol respectively...
2016: BMC Veterinary Research
Cuyue Tang, Hong Jin, Sudarshan Kapadnis, Ting Chen, Dooyoung Lee, Andrew McRiner, Andrew Cook, Duane A Burnett, Gerhard Koenig
Three quinuclidine derivatives (FRM-1, FRM-2 and FRM-3) were subject to significant cellular retention as evidenced by low mass recovery in Caco-2 permeation experiments. The mass recovery deteriorated with incubation time and was direction dependent. According to the apparent permeability coefficient calculated with the conventional 'sink' method (P<sub>app,sink</sub>), the efflux ratio (ER) is close to unity for FRM-1, and approximately 2 and 3.5 for FRM 2 and FRM 3. Treatment with bafilomycin A1 (BFA, 100 nM) did not appreciably change the mass recovery for FRM-2, but considerably enhanced it for FRM-1 and FRM-3, leading to an increase in P<sub>app</sub> by 5- and 2-fold with a negligible impact on ER values...
July 25, 2016: Drug Metabolism Letters
Dipy M Vasa, Ira S Buckner, Jane E Cavanaugh, Peter L D Wildfong
Epithelial flux and permeability across bovine olfactory tissue were compared when levodopa (L-DOPA) was loaded in different physical states. Aqueous solution of L-DOPA was prepared in Krebs-Ringer buffer (KRB), at a concentration (0.75 mg/mL) verified to be less than the saturation solubility at both 25 and 37°C. Sodium metabisulfite was added to solution to minimize L-DOPA oxidation; chemical stability of aqueous L-DOPA was evaluated using HPLC-UV. Solid-state characterization of unprocessed, dry, crystalline L-DOPA powder was performed using TGA, DSC, PXRD, and optical microscopy to ensure that preparation of L-DOPA microparticles used for diffusion experiments did not elicit a phase change...
July 5, 2016: AAPS PharmSciTech
Qian Chu, Jolene K Diedrich, Joan M Vaughan, Cynthia J Donaldson, Michael F Nunn, Kuo-Fen Lee, Alan Saghatelian
Apolipoprotein E (ApoE) belongs to a large class of proteins that solubilize lipids for physiological transport. Humans have three different APOE alleles, APOE ε2, APOE ε3, and APOE ε4, and genetic studies identified ApoE4 as the strongest genetic risk factor for Alzheimer's disease (AD). People who are homozygous for ApoE4 (i.e., ApoE4/E4) are an order of magnitude more likely to develop late-onset AD (LOAD) than ApoE3/E3 carriers. Several differences between ApoE3 and ApoE4 may contribute to AD including the observation that ApoE4 is degraded to a greater extent than ApoE3 in the human brain...
August 3, 2016: Journal of the American Chemical Society
Sonia Abad, Carla Ramon, David Pubill, Jorge Camarasa, Antonio Camins, Elena Escubedo
MDMA is one of the most used drugs by adolescents and its consumption has been associated with many psychobiological problems, among them psychomotor problems. Moreover, some authors described that early exposure to MDMA may render the dopaminergic neurons more vulnerable to the effects of future neurotoxic insults. Alzheimer disease (AD) is the main cause of dementia in the elderly and a percentage of the patients have predisposition to suffer nigrostriatal alterations, developing extrapyramidal signs. Nigrostriatal dysfunction in the brain of aged APPswe/PS1dE9 (APP/PS1), a mouse model of familiar AD (FAD), has also been described...
September 2016: Biochimica et Biophysica Acta
Kasper P Kepp
Alzheimer's Disease (AD) is a highly complex disease involving a broad range of clinical, cellular, and biochemical manifestations that are currently not understood in combination. This has led to many views of AD, e.g. the amyloid, tau, presenilin, oxidative stress, and metal hypotheses. The amyloid hypothesis has dominated the field with its assumption that buildup of pathogenic β-amyloid (Aβ) peptide causes disease. This paradigm has been criticized, yet most data suggest that Aβ plays a key role in the disease...
August 2016: Progress in Neurobiology
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