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APP transport

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https://www.readbyqxmd.com/read/29128960/a-proteomics-analysis-reveals-9-up-regulated-proteins-associated-with-altered-cell-signaling-in-colon-cancer-patients
#1
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
https://www.readbyqxmd.com/read/29118375/the-lipid-raft-dwelling-protein-us9-can-be-manipulated-to-target-app-compartmentalization-app-processing-and-neurodegenerative-disease-pathogenesis
#2
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
https://www.readbyqxmd.com/read/29105065/reduced-blood-brain-barrier-expression-of-fatty-acid-binding-protein-5-is-associated-with-increased-vulnerability-of-app-ps1-mice-to-cognitive-deficits-from-low-omega-3-fatty-acid-diets
#3
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 AD transgenic mice (APPswe,PSEN1∆E9) relative to wild-type, associated with a 34.5 ± 6.7% reduction in FABP5 expression in isolated brain capillaries of AD mice...
November 3, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29093025/phosphorylation-of-klc1-modifies-interaction-with-jip1-and-abolishes-the-enhanced-fast-velocity-of-app-transport-by-kinesin-1
#4
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
https://www.readbyqxmd.com/read/29093024/phosphorylation-of-multiple-sites-within-an-acidic-region-of-alcadein-%C3%AE-is-required-for-kinesin-1-association-and-golgi-exit-of-alcadein-%C3%AE-cargo
#5
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
https://www.readbyqxmd.com/read/29079999/trafficking-in-alzheimer-s-disease-modulation-of-app-transport-and-processing-by-the-transmembrane-proteins-lrp1-sorla-sorcs1c-sortilin-and-calsyntenin
#6
REVIEW
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
https://www.readbyqxmd.com/read/29078331/lack-of-bace1-s-palmitoylation-reduces-amyloid-burden-and-mitigates-memory-deficits-in-transgenic-mouse-models-of-alzheimer-s-disease
#7
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...
October 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29066623/reconciling-contradictory-findings-glucose-transporter-1-glut1-functions-as-an-oligomer-of-allosteric-alternating-access-transporters
#8
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
https://www.readbyqxmd.com/read/29066369/astrocytic-glutamatergic-transporters-are-involved-in-a%C3%AE-induced-synaptic-dysfunction
#9
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
https://www.readbyqxmd.com/read/29063555/representing-knowledge-consistently-across-health-systems
#10
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
https://www.readbyqxmd.com/read/29058763/s14g-humanin-alleviates-insulin-resistance-and-increases-autophagy-in-neurons-of-app-ps1-transgenic-mouse
#11
Kun Han, Ning Jia, Yi Zhong, Xiuli Shang
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by Aβ plaque deposition in the brain, which is related to the disorder of autophagosome maturation, transport and formation of autolysosome. Notably, abnormal insulin signaling is connected with cognitive dysfunction in AD. In this study, using APP/PS1 transgenic mice as AD model, we investigated the mechanism by which S14G-humanin (HNG) improved autophagy and insulin signaling in AD brain. Immunohistochemistry was used to determine the levels of mTOR and Aβ deposition, and Western blot analysis was used to determine IRS-1, IRS-1 pSEr636, ULK1, p62, LC3 I/LC3 II protein levels...
October 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29046271/client-focused-security-assessment-of-mhealth-apps-and-recommended-practices-to-prevent-or-mitigate-transport-security-issues
#12
Jannis Müthing, Thomas Jäschke, Christoph M Friedrich
BACKGROUND: Mobile health (mHealth) apps show a growing importance for patients and health care professionals. Apps in this category are diverse. Some display important information (ie, drug interactions), whereas others help patients to keep track of their health. However, insufficient transport security can lead to confidentiality issues for patients and medical professionals, as well as safety issues regarding data integrity. mHealth apps should therefore deploy intensified vigilance to protect their data and integrity...
October 18, 2017: JMIR MHealth and UHealth
https://www.readbyqxmd.com/read/29028815/striatal-astrocytes-engulf-dopaminergic-debris-in-parkinson-s-disease-a-study-in-an-animal-model
#13
Ingrid Morales, Alberto Sanchez, Clara Rodriguez-Sabate, Manuel Rodriguez
The role of astrocytes in Parkinson's disease is still not well understood. This work studied the astrocytic response to the dopaminergic denervation. Rats were injected in the lateral ventricles with 6-hydroxydopamine (25μg), inducing a dopaminergic denervation of the striatum not accompanied by non-selective tissue damage. The dopaminergic debris were found within spheroids (free-spheroids) which retained some proteins of dopaminergic neurons (e.g., tyrosine hydroxylase, the dopamine transporter protein, and APP) but not others (e...
2017: PloS One
https://www.readbyqxmd.com/read/28956068/amyloid-precursor-protein-products-concentrate-in-a-subset-of-exosomes-specifically-endocytosed-by-neurons
#14
Karine Laulagnier, Charlotte Javalet, Fiona J Hemming, Mathilde Chivet, Gaëlle Lachenal, Béatrice Blot, Christine Chatellard, Rémy Sadoul
Amyloid beta peptide (Aβ), the main component of senile plaques of Alzheimer's disease brains, is produced by sequential cleavage of amyloid precursor protein (APP) and of its C-terminal fragments (CTFs). An unanswered question is how amyloidogenic peptides spread throughout the brain during the course of the disease. Here, we show that small lipid vesicles called exosomes, secreted in the extracellular milieu by cortical neurons, carry endogenous APP and are strikingly enriched in CTF-α and the newly characterized CTF-η...
September 27, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28955508/mobile-real-time-tracking-of-acute-stroke-patients-and-instant-secure-inter-team-communication-the-join-app
#15
Stephan A Munich, Lee A Tan, Danilo M Nogueira, Kiffon M Keigher, Michael Chen, R Webster Crowley, James J Conners, Demetrius K Lopes
PURPOSE: The primary correlate to survival and preservation of neurologic function in patients suffering from an acute ischemic stroke is time from symptom onset to initiation of therapy and reperfusion. Communication and coordination among members of the stroke team are essential to maximizing efficiency and subsequently early reperfusion. In this work, we aim to describe our preliminary experience using the Join mobile application as a means to improve interdisciplinary team communication and efficiency...
September 2017: Neurointervention
https://www.readbyqxmd.com/read/28952054/disease-induced-alterations-in-brain-drug-transporters-in-animal-models-of-alzheimer-s-disease
#16
Kati-Sisko Vellonen, Jouni Ihalainen, Marie-Christine Boucau, Fabien Gosselet, Théo Picardat, Mikko Gynther, Katja M Kanninen, Anthony R White, Tarja Malm, Jari Koistinaho, Markus M Forsberg, Marika Ruponen
PURPOSE: Alzheimer's disease (AD) may disturb functions of the blood-brain barrier and change the disposition of drugs to the brain. This study assessed the disease-induced changes in drug transporters in the brain capillaries of transgenic AD mice. METHODS: Eighteen drug transporters and four tight junction-associated proteins were analyzed by RT-qPCR in cortex, hippocampus and cerebellum tissue samples of 12-16-month-old APdE9, Tg2576 and APP/PS1 transgenic mice and their healthy age-matched controls...
September 26, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28946017/par3-and-apkc-regulate-bace1-endosome-to-tgn-trafficking-through%C3%A2-pacs1
#17
Miao Sun, Huaye Zhang
The cleavage of amyloid precursor protein (APP) by β-site APP cleaving enzyme 1 (BACE1) is the rate-limiting step in beta amyloid generation during Alzheimer's disease (AD) pathogenesis. In AD brains, BACE1 is abnormally accumulated in endocytic compartments, where the acidic pH is optimal for its activity. However, mechanisms regulating the endosome-to-trans-Golgi network (TGN) retrieval of BACE1 remain unclear. Here, we show that partitioning defective 3 (Par3) facilitates BACE1 retrograde trafficking from endosomes to the TGN...
December 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28941799/regulatory-effects-of-simvastatin-and-apoj-on-app-processing-and-amyloid-%C3%AE-clearance-in-blood-brain-barrier-endothelial-cells
#18
Martina Zandl-Lang, Elham Fanaee-Danesh, Yidan Sun, Nicole M Albrecher, Chaitanya Chakravarthi Gali, Igor Čančar, Alexandra Kober, Carmen Tam-Amersdorfer, Anika Stracke, Steffen M Storck, Ahmed Saeed, Jasminka Stefulj, Claus U Pietrzik, Mark R Wilson, Ingemar Björkhem, Ute Panzenboeck
Amyloid-β peptides (Aβ) accumulate in cerebral capillaries indicating a central role of the blood-brain barrier (BBB) in the pathogenesis of Alzheimer's disease (AD). Although a relationship between apolipoprotein-, cholesterol- and Aβ metabolism is evident, the interconnecting mechanisms operating in brain capillary endothelial cells (BCEC) are poorly understood. ApoJ (clusterin) is present in HDL that regulates cholesterol metabolism which is disturbed in AD. ApoJ levels are increased in AD brains and in plasma of cerebral amyloid angiopathy (CAA) patients...
September 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28899417/serotonin-augmentation-therapy-by-escitalopram-has-minimal-effects-on-amyloid-%C3%AE-levels-in-early-stage-alzheimer-s-like-disease-in-mice
#19
Christian Ulrich von Linstow, Jonas Waider, Manuela Grebing, Athanasios Metaxas, Klaus Peter Lesch, Bente Finsen
BACKGROUND: Dysfunction of the serotonergic (5-HTergic) system has been implicated in the cognitive and behavioural symptoms of Alzheimer's disease (AD). Accumulation of toxic amyloid-β (Aβ) species is a hallmark of AD and an instigator of pathology. Serotonin (5-HT) augmentation therapy by treatment with selective serotonin reuptake inhibitors (SSRIs) in patients with AD has had mixed success in improving cognitive function, whereas SSRI administration to mice with AD-like disease has been shown to reduce Aβ pathology...
September 12, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28899359/transcript-profiling-of-the-immunological-interactions-between-actinobacillus-pleuropneumoniae-serotype-7-and-the-host-by-dual-rna-seq
#20
Ping Li, Zhiwen Xu, Xiangang Sun, Yue Yin, Yi Fan, Jun Zhao, Xiyu Mao, Jianbo Huang, Fan Yang, Ling Zhu
BACKGROUND: The complexity of the pathogenic mechanism underlying the host immune response to Actinobacillus pleuropneumonia (App) makes the use of preventive measures difficult, and a more global view of the host-pathogen interactions and new insights into this process are urgently needed to reveal the pathogenic and immune mechanisms underlying App infection. Here, we infected specific pathogen-free Mus musculus with App serotype 7 by intranasal inoculation to construct an acute hemorrhagic pneumonia infection model and isolated the infected lungs for analysis of the interactions by dual RNA-seq...
September 12, 2017: BMC Microbiology
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