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APP transport

Chaoqun Wang, Yikai Shou, Jie Pan, Yue Du, Cuiqing Liu, Huanhuan Wang
Globally, Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the elderly population, the hallmark of which is amyloid β (Aβ) peptide. Energy metabolism and AD pathogenesis are believed to influence one another. Different cholesterol levels are thought to influence various steps in neurotoxic Aβ generation, including amyloid precursor protein (APP) proteolysis and the corresponding activities of α-, β-, and γ-secretases. In addition, cholesterol has been proved to mediate Aβ metabolism, such as its fibrillation, transportation, degradation, and clearance processes...
January 11, 2018: Nutritional Neuroscience
Tingting Zheng, Xiaoqing Wu, Xiaojie Wei, Mingkai Wang, Baorong Zhang
Amyloid precursor protein (APP) processing is central in Alzheimer's disease (AD) pathogenesis. The healthy unaffected neurons suffer the transmission of amyloid protein from pathologically affected neurons, which may play an important role in the anatomical spread of the disease. Exosomes are appropriate candidates for transmission of amyloid species, because of their potential role as "intercellular transportation". To address a role of secreted exosomes in neuronal homeostasis in AD, we harvested exosomes from the conditioned medium of HEK293-APP Swe/Ind cells...
December 22, 2017: Neurochemistry International
Masanori Tachikawa, Shirou Hirose, Shin-Ichi Akanuma, Ryo Matsuyama, Ken-Ichi Hosoya
l-Arginine is required for regulating synapse formation/patterning and angiogenesis in the developing brain. We hypothesized that this requirement would be met by increased transporter-mediated supply across the blood-brain barrier (BBB). Thus, the purpose of this work was to test the idea that elevation of blood-to-brain l-arginine transport across the BBB in the postnatal period coincides with up-regulation of cationic acid transporter 1 (CAT1) expression in developing brain capillaries. We found that the apparent brain-to-plasma concentration ratio (Kp, app) of l-arginine after intravenous administration during the first and second postnatal weeks was 2-fold greater than that at the adult stage...
December 13, 2017: Microvascular Research
Yue Wang, Pei-Pei Guan, Xin Yu, Yan-Su Guo, Ying-Jie Zhang, Zhan-You Wang, Pu Wang
Although the roles of cyclooxygenase-2 (COX-2) and prostaglandins (PGs) in regulating amyloid precursor protein (APP) cleavage and β-amyloid protein (Aβ) production have been the subjects of numerous investigations, their effects on tau phosphorylation have been largely overlooked. Using human TauP301S transgenic (Tg) mice as in vivo model, our results demonstrated that PGI2 and PGF2α mediated the effects of tumor necrosis factor α (TNF-α) and Zinc ions (Zn2+) on upregulating the phosphorylation of tau via the PI3-K/AKT, ERK1/2 and JNK/c-Jun signaling pathways...
November 21, 2017: Oncotarget
Gavirangappa Hithamani, Dhanya Kizhakayil, Krishnapura Srinivasan
In continuation of our studies on the bioaccessibility of phenolic compounds from food grains as influenced by domestic processing, we examined the uptake of phenolics from native/sprouted finger millet (Eleucine coracana) and green gram (Vigna radiata) and native/heat-processed onion (Allium cepa) in human Caco-2 cells. Absorption of pure phenolic compounds, as well as the uptake of phenolic compounds from finger millet, green gram, and onion, was investigated in Caco-2 monolayer model. Transport of individual phenolic compounds from apical compartment to the basolateral compartment across Caco-2 monolayer was also investigated...
December 2017: Journal of Biosciences
Melissa Bopp, Dangaia Sims, Stephen A Matthews, Liza S Rovniak, Erika Poole, Joanna Colgan
PURPOSE: To outline the development, implementation, and evaluation of a multistrategy intervention to promote active transportation, on a large university campus. DESIGN: Single group pilot study. SETTING: A large university in the Northeastern United States. PARTICIPANTS: University students (n = 563), faculty and staff (employees, n = 999) were included in the study. INTERVENTION: The Active Lions campaign aimed to increase active transportation to campus for all students and employees...
January 1, 2017: American Journal of Health Promotion: AJHP
Stephen R Mitroff, Justin M Ericson, Benjamin Sharpe
Objective The study's objective was to assess a new personnel selection and assessment tool for aviation security screeners. A mobile app was modified to create a tool, and the question was whether it could predict professional screeners' on-job performance. Background A variety of professions (airport security, radiology, the military, etc.) rely on visual search performance-being able to detect targets. Given the importance of such professions, it is necessary to maximize performance, and one means to do so is to select individuals who excel at visual search...
November 1, 2017: Human Factors
Hong-Xin Fei, Ying-Bo Zhang, Ting Liu, Xiao-Jie Zhang, Shu-Liang Wu
Alzheimer's disease (AD) is the most common cause of dementia among elderly population. Deranged β-amyloid (Aβ) trafficking across the blood-brain barrier is known to be a critical element in the pathogenesis of AD. In the vascular endothelial cells of hippocampus, Aβ transport is mainly mediated by low-density lipoprotein-associated protein 1 (LRP1) and the receptor for advanced glycation end (RAGE) products; therefore, LRP1 and RAGE endothelial cells are potential therapeutic targets for AD. In this study, we explored the effects of Formononetin (FMN) on learning and memory improvement in APP/PS1 mice and the related mechanisms...
December 1, 2017: Bioscience, Biotechnology, and Biochemistry
Jung-Ah Lee, Hannah Nguyen, Joan Park, Linh Tran, Trang Nguyen, Yen Huynh
Objectives: Families of ethnic minority persons with dementia often seek help at later stages of the disease. Little is known about the effectiveness of various methods in supporting ethnic minority dementia patients' caregivers. The objective of the study was to identify smartphone and computer usage among family caregivers of dementia patients (i.e., Korean and Vietnamese Americans) to develop dementia-care education programs for them. Methods: Participants were asked various questions related to their computer or smartphone usage in conjunction with needs-assessment interviews...
October 2017: Healthcare Informatics Research
Gesine Benze, Friedemann Nauck, Bernd Alt-Epping, Giuseppe Gianni, Thomas Bauknecht, Johannes Ettl, Anna Munte, Luisa Kretzschmar, Jan Gaertner
BACKGROUND: In advanced cancer, quality of life (QoL) is a major treatment goal. In order to achieve this, the identification of suffering by screening for patient-reported-outcomes (PROs, i.e., symptoms) is of utmost importance. The use of paper-pencil questionnaires is associated with significant shortcomings due to missing data, recall bias and transcription errors. Other than that, the electronic recording of PROs by mobile Health (mHealth) offers a number of advantages. The aim of this study was to test whether the routine assessment of PROs via a newly developed smartphone application (MeQoL®) is feasible...
October 26, 2017: Annals of Palliative Medicine
Oleg I Kit, Dmitry I Vodolazhsky, Denis S Kutilin, Yaroslav S Enin, Yury A Gevorkyan, Peter V Zolotukhin, Yanis Boumber, Leonid V Kharin, Svetlana B Panina
Colorectal cancer is the second most common cancer in women and third most common cancer in men. Cell signaling alterations in colon cancer, especially in aggressive metastatic tumors, require further investigations. The present study aims to compare the expression pattern of proteins associated with cell signaling in paired tumor and non-tumor samples of patients with colon cancer, as well as to define the cluster of proteins to differentiate patients with non-metastatic (Dukes' grade B) and metastatic (Dukes' grade C&D) colon cancer...
November 11, 2017: Protein Journal
Renato Brandimarti, Gordon S Hill, Jonathan D Geiger, Olimpia Meucci
The trafficking behavior of the lipid raft-dwelling US9 protein from Herpes Simplex Virus strikingly overlaps with that of the amyloid precursor protein (APP). Both US9 and APP processing machinery rely on their ability to shuttle between endosomes and plasma membranes, as well as on their lateral accumulation in lipid rafts. Therefore, repurposing US9 to track/modify these molecular events represents a valid approach to investigate pathological states including Alzheimer's disease and HIV-associated neurocognitive disorders where APP misprocessing to amyloid beta formation has been observed...
November 8, 2017: Scientific Reports
Yijun Pan, Kwok H C Choy, Philip J Marriott, Siew Y Chai, Martin J Scanlon, Christopher J H Porter, Jennifer L Short, Joseph A Nicolazzo
Lower levels of the cognitively beneficial docosahexaenoic acid (DHA) are often observed in Alzheimer's disease (AD) brains. Brain DHA levels are regulated by the blood-brain barrier (BBB) transport of plasma-derived DHA, a process facilitated by fatty acid-binding protein 5 (FABP5). This study reports a 42.1 ± 12.6% decrease in the BBB transport of 14 C-DHA in 8-month-old AD transgenic mice (APPswe,PSEN1∆E9) relative to wild-type mice, associated with a 34.5 ± 6.7% reduction in FABP5 expression in isolated brain capillaries of AD mice...
January 2018: Journal of Neurochemistry
Kyoko Chiba, Ko-Yi Chien, Yuriko Sobu, Saori Hata, Shun Kato, Tadashi Nakaya, Yasushi Okada, Angus C Nairn, Masataka Kinjo, Hidenori Taru, Rong Wang, Toshiharu Suzuki
In neurons, amyloid β-protein precursor (APP) is transported by binding to kinesin-1, mediated by JNK-interacting protein 1b (JIP1b), which generates the enhanced fast velocity (EFV) and efficient high frequency (EHF) of APP anterograde transport. Previously we showed that EFV requires a conventional interaction between JIP1b C-terminal region and kinesin light chain 1 (KLC1) tetratricopeptide repeat, whereas EHF requires a novel interaction between the central region of JIP1b and the coiled-coil domain of KLC1...
November 1, 2017: Molecular Biology of the Cell
Yuriko Sobu, Keiko Furukori, Kyoko Chiba, Angus C Nairn, Masataka Kinjo, Saori Hata, Toshiharu Suzuki
Alcadein α (Alcα) is a major cargo of kinesin-1 that is subjected to anterograde transport in neuronal axons. Two tryptophan- and aspartic acid-containing (WD) motifs located in its cytoplasmic domain directly bind the tetratricopeptide repeat (TPR) motifs of kinesin light chain (KLC), which activate kinesin-1 and recruit kinesin-1 to Alcα cargo. We found that phosphorylation of three serine residues in the acidic region located between the two WD motifs is required for interaction with KLC. Phosphorylation of these serine residues may alter the disordered structure of the acidic region to induce the direct association with KLC...
November 1, 2017: Molecular Biology of the Cell
Simone Eggert, Carolin Thomas, Stefan Kins, Guido Hermey
The amyloid precursor protein (APP), one key player in Alzheimer's disease (AD), is extensively processed by different proteases. This leads to the generation of diverging fragments including the amyloid β (Aβ) peptide, which accumulates in brains of AD patients. Subcellular trafficking of APP is an important aspect for its proteolytic conversion, since the various secretases which cleave APP are located in different cellular compartments. As a consequence, altered subcellular targeting of APP is thought to directly affect the degree to which Aβ is generated...
October 27, 2017: Molecular Neurobiology
Robert J Andrew, Celia G Fernandez, Molly Stanley, Hong Jiang, Phuong Nguyen, Richard C Rice, Virginie Buggia-Prévot, Pierre De Rossi, Kulandaivelu S Vetrivel, Raza Lamb, Arnau Argemi, Emilie S Allaert, Elle M Rathbun, Sofia V Krause, Steven L Wagner, Angèle T Parent, David M Holtzman, Gopal Thinakaran
Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by pathological brain lesions and a decline in cognitive function. β-Amyloid peptides (Aβ), derived from proteolytic processing of amyloid precursor protein (APP), play a central role in AD pathogenesis. β-Site APP cleaving enzyme 1 (BACE1), the transmembrane aspartyl protease which initiates Aβ production, is axonally transported in neurons and accumulates in dystrophic neurites near cerebral amyloid deposits in AD. BACE1 is modified by S-palmitoylation at four juxtamembrane cysteine residues...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
Kenneth P Lloyd, Ogooluwa A Ojelabi, Julie K De Zutter, Anthony Carruthers
Recent structural studies suggest that glucose transporter 1 (GLUT1)-mediated sugar transport is mediated by an alternating access transporter that successively presents exofacial (e2) and endofacial (e1) substrate-binding sites. Transport studies, however, indicate multiple, interacting (allosteric), and co-existent, exo- and endofacial GLUT1 ligand-binding sites. The present study asks whether these contradictory conclusions result from systematic analytical error or reveal a more fundamental relationship between transporter structure and function...
October 24, 2017: Journal of Biological Chemistry
Shuxuan Huang, Huichun Tong, Ming Lei, Miaomiao Zhou, Wenyuan Guo, Guihua Li, Xiaolu Tang, Zhe Li, Mingshu Mo, Xiuping Zhang, Xiang Chen, Luan Cen, Lei Wei, Yousheng Xiao, Kaiping Li, Qinghui Huang, Xinling Yang, Weiguo Liu, Li Zhang, Shaogang Qu, Shaomin Li, Pingyi Xu
In Alzheimer's disease (AD), dementia severity correlates most strongly with decreased synapse density in the hippocampus and cerebral cortex. Although studies in rodents have established that hippocampal long-term potentiation (LTP) is inhibited by soluble oligomers of beta-amyloid (Aβ), the synaptic mechanisms remain unclear. Here, field excitatory postsynaptic potentials (fEPSP) recordings were made in the CA1 region of mouse hippocampal slices. The medium of APP-expressing CHO cells, which contain soluble forms of Aβ including small oligomers, inhibited LTP and facilitated long-term depression (LTD), thus making the LTP/LTD curve shift toward the right...
October 21, 2017: Brain Research
S T Rosenbloom, R J Carroll, J L Warner, M E Matheny, J C Denny
Objectives: Electronic health records (EHRs) have increasingly emerged as a powerful source of clinical data that can be leveraged for reuse in research and in modular health apps that integrate into diverse health information technologies. A key challenge to these use cases is representing the knowledge contained within data from different EHR systems in a uniform fashion. Method: We reviewed several recent studies covering the knowledge representation in the common data models for the Observational Medical Outcomes Partnership (OMOP) and its Observational Health Data Sciences and Informatics program, and the United States Patient Centered Outcomes Research Network (PCORNet)...
August 2017: Yearbook of Medical Informatics
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