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amyloid precursor protein

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https://www.readbyqxmd.com/read/28811745/inhibition-of-inflammation-mediated-through-the-tumor-necrosis-factor-%C3%AE-biochemical-pathway-can-lead-to-favorable-outcomes-in-alzheimer-disease
#1
REVIEW
Daniah Shamim, Michael Laskowski
Tumor necrosis factor α (TNF-α) inhibitors have long been used as disease-modifying agents in immune disorders. Recently, research has shown a role of chronic neuroinflammation in the pathophysiology of neurodegenerative diseases such as Alzheimer disease, and interest has been generated in the use of anti-TNF agents and TNF-modulating agents for prevention and treatment. This article extensively reviewed literature on animal studies testing these agents. The results showed a role for direct and indirect TNF-α inhibition through agents such as thalidomide, 3,6-dithiothalidomide, etanercept, infliximab, exendin-4, sodium hydrosulfide, minocycline, imipramine, and atorvastatin...
2017: Journal of Central Nervous System Disease
https://www.readbyqxmd.com/read/28811582/a-new-class-of-hybrid-secretion-system-is-employed-in-pseudomonas-amyloid-biogenesis
#2
Sarah L Rouse, William J Hawthorne, Jamie-Lee Berry, Dror S Chorev, Sandra A Ionescu, Sebastian Lambert, Fisentzos Stylianou, Wiebke Ewert, Uma Mackie, R Marc L Morgan, Daniel Otzen, Florian-Alexander Herbst, Per H Nielsen, Morten Dueholm, Hagan Bayley, Carol V Robinson, Stephen Hare, Stephen Matthews
Gram-negative bacteria possess specialised biogenesis machineries that facilitate the export of amyloid subunits for construction of a biofilm matrix. The secretion of bacterial functional amyloid requires a bespoke outer-membrane protein channel through which unfolded amyloid substrates are translocated. Here, we combine X-ray crystallography, native mass spectrometry, single-channel electrical recording, molecular simulations and circular dichroism measurements to provide high-resolution structural insight into the functional amyloid transporter from Pseudomonas, FapF...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28809040/a-mobile-app-for-sharing-contacts-on-your-cell-an-editorial-highlight-for-the-physiological-role-of-the-amyloid-precursor-protein-app-as-an-adhesion-molecule-in-the-developing-nervous-system-on-doi-10-1111-jnc-14122
#3
EDITORIAL
George William Rebeck, Daniel T S Pak
This is an Editorial for a review that Sosa and coworkers present in the current issue of the Journal of Neurochemistry of physiological functions for amyloid precursor protein (APP) at dynamic cellular contact sites such as growth cones, neuronal migration tracts, and synapses. Here, APP physically links the extracellular and intracellular milieus through a multitude of binding partners. From these observations, the authors offer a model of APP as a cell adhesion molecule in the brain, providing a context for understanding its role in Alzheimer's disease and Down syndrome...
August 15, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28799137/ethanol-alters-app-processing-and-aggravates-alzheimer-associated-phenotypes
#4
Daochao Huang, Mengjiao Yu, Shou Yang, Dandan Lou, Weitao Zhou, Lingling Zheng, Zhe Wang, Fang Cai, Weihui Zhou, Tingyu Li, Weihong Song
The majority of Alzheimer's disease (AD) cases are sporadic with unknown causes. Many dietary factors including excessive alcohol intake have been reported to increase the risk to develop AD. The effect of alcohol on cognitive functions and AD pathogenesis remains elusive. In this study, we investigated the relationship between ethanol exposure and Alzheimer's disease. Cell cultures were treated with ethanol at different dosages for different durations up to 48 h and an AD model mouse was fed with ethanol for 4 weeks...
August 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28799085/dimerization-leads-to-changes-in-app-amyloid-precursor-protein-trafficking-mediated-by-lrp1-and-sorla
#5
Simone Eggert, A C Gonzalez, C Thomas, S Schilling, S M Schwarz, C Tischer, V Adam, P Strecker, V Schmidt, T E Willnow, G Hermey, C U Pietrzik, E H Koo, Stefan Kins
Proteolytic cleavage of the amyloid precursor protein (APP) by α-, β- and γ-secretases is a determining factor in Alzheimer's disease (AD). Imbalances in the activity of all three enzymes can result in alterations towards pathogenic Aβ production. Proteolysis of APP is strongly linked to its subcellular localization as the secretases involved are distributed in different cellular compartments. APP has been shown to dimerize in cis-orientation, affecting Aβ production. This might be explained by different substrate properties defined by the APP oligomerization state or alternatively by altered APP monomer/dimer localization...
August 10, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28798667/the-foxp2-driven-network-in-developmental-disorders-and-neurodegeneration
#6
Franz Oswald, Patricia Klöble, André Ruland, David Rosenkranz, Bastian Hinz, Falk Butter, Sanja Ramljak, Ulrich Zechner, Holger Herlyn
The transcription repressor FOXP2 is a crucial player in nervous system evolution and development of humans and songbirds. In order to provide an additional insight into its functional role we compared target gene expression levels between human neuroblastoma cells (SH-SY5Y) stably overexpressing FOXP2 cDNA of either humans or the common chimpanzee, Rhesus monkey, and marmoset, respectively. RNA-seq led to identification of 27 genes with differential regulation under the control of human FOXP2, which were previously reported to have FOXP2-driven and/or songbird song-related expression regulation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28796251/differential-spatial-expression-of-peripheral-olfactory-neuron-derived-bace1-induces-olfactory-impairment-by-region-specific-accumulation-of-%C3%AE-amyloid-oligomer
#7
Seung-Jun Yoo, Ji-Hye Lee, So Yeun Kim, Gowoon Son, Jae Yeon Kim, Bongki Cho, Seong-Woon Yu, Keun-A Chang, Yoo-Hun Suh, Cheil Moon
Olfactory dysfunction is a common symptom associated with neurodegenerative diseases including Alzheimer's disease (AD). Although evidence exists to suggest that peripheral olfactory organs are involved in the olfactory dysfunction that accompanies AD pathology, the underlying mechanisms are not fully understood. As confirmed using behavioral tests, transgenic mice overexpressing a Swedish mutant form of human amyloid precursor proteins exhibited olfactory impairments prior to evidence of cognitive impairment...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28796060/candidate-genes-investigation-for-severe-nonalcoholic-fatty-liver-disease-based-on-bioinformatics-analysis
#8
Shan Qi, Changhong Wang, Chunfu Li, Pu Wang, Minghui Liu
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition worldwide. However, its etiology and fundamental pathophysiology for the disease process are poorly understood. In this study, we thus used bioinformatics to identify candidate genes potentially causative of severe NAFLD. METHODS: Gene expression profile data GSE49541 were downloaded from the Gene Expression Omnibus database. Tissues samples from 32 severe and 40 mild NAFLD patients were evaluated to identify differentially expressed genes (DEGs) between the 2 groups, followed by analyses of Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes pathways...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28791490/secretases-related-mirnas-in-alzheimer-s-disease-new-approach-for-biomarker-discovery
#9
REVIEW
Seyedeh Nazanin Hajjari, Mehdi Mehdizadeh, Saeed Sadigh-Eteghad, Dariush Shanehbandi, Shahram Teimourian, Behzad Baradaran
Amyloid-β (Aβ) as a crucial factor in pathogenesis of Alzheimer's disease (AD) is derived from amyloid precursor protein (APP) through a proteolytic process catalyzing by β- and γ-secretase-in amyloidogenesis pathway. Products of α-secretase cleavage also have protective effects against Aβ toxicity. According to existing evidences, microRNAs (miRNAs) show a unique pattern of expression in AD. Moreover, miRNAs regulatory effects on expression of secretases and their main components have been demonstrated in AD...
August 8, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28791165/a-biomimetic-semisynthesis-enables-structural-elucidation-of-selaginellin-u-a-tautomeric-cyclic-alkynylphenol-from-selaginella-tamariscina
#10
Qin-Feng Zhu, Ying Bao, Zhi-Jun Zhang, Jia Su, Li-Dong Shao, Qin-Shi Zhao
Two new lactone-containing selaginellins T and U (1 and 2) together with eleven known selaginellin derivatives (3 and 7-16) were isolated from the whole plant of Selaginella tamariscina. The structure of tautomeric selaginellin U along with its biogenetic pathway was confirmed and proposed by a cross-validation of the semisynthesis of compound 4 from selaginellin (3) and derivation from 2 to 4. Additionally, compounds 3, 13 and 16 exhibited good inhibitory activities against β-site amyloid precursor protein cleaving enzyme 1 (BACE1) with IC50 values of 81...
July 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28790893/brain-and-peripheral-atypical-inflammatory-mediators-potentiate-neuroinflammation-and-neurodegeneration
#11
REVIEW
Duraisamy Kempuraj, Ramasamy Thangavel, Govindhasamy P Selvakumar, Smita Zaheer, Mohammad E Ahmed, Sudhanshu P Raikwar, Haris Zahoor, Daniyal Saeed, Prashant A Natteru, Shankar Iyer, Asgar Zaheer
Neuroinflammatory response is primarily a protective mechanism in the brain. However, excessive and chronic inflammatory responses can lead to deleterious effects involving immune cells, brain cells and signaling molecules. Neuroinflammation induces and accelerates pathogenesis of Parkinson's disease (PD), Alzheimer's disease (AD) and Multiple sclerosis (MS). Neuroinflammatory pathways are indicated as novel therapeutic targets for these diseases. Mast cells are immune cells of hematopoietic origin that regulate inflammation and upon activation release many proinflammatory mediators in systemic and central nervous system (CNS) inflammatory conditions...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28790170/dimerization-of-the-transmembrane-domain-of-amyloid-precursor-protein-is-determined-by-residues-around-the-gamma-secretase-cleavage-sites
#12
Yan Yan, Ting-Hai Xu, Kaleeckal G Harikumar, Laurence J Miller, Karsten Melcher, H Eric Xu
One of the hallmarks of Alzheimer's disease (AD) is the formation of extracellular amyloid plaques that consist mainly of abnormally aggregated forms of amyloid β (Aβ) peptides. These peptides are generated by γ-secretase-catalyzed cleavage of a dimeric membrane-bound C-terminal fragment (C99) of the amyloid precursor protein (APP). While C99 homodimerization has been linked to Aβ; production and changes in the aggregation-determining Aβ42/Aβ40 ratio, the motif through which C99 dimerizes has remained controversial...
August 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28789837/investigating-the-amyloid-beta-enhancing-effect-of-cgmp-in-neuro2a-cells
#13
Elisa Calcagno, Francesca Caudano, Mario Passalacqua, Maria A Pronzato, Ernesto Fedele, Roberta Ricciarelli
Long-term potentiation (LTP) and the process of memory formation require activation of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) pathways. Notably, recent evidence indicated that both cyclic nucleotides boost the production of amyloid-beta (Aβ) peptides. In particular, cAMP was shown to favor hippocampal LTP by stimulating the synthesis of the amyloid precursor protein APP, whereas cGMP was found to enhance LTP and to improve memory by increasing Aβ levels without affecting the expression of APP...
August 5, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28781776/unraveling-the-genes-implicated-in-alzheimer-s-disease
#14
Mohan Giri, Abhilasha Shah, Bibhuti Upreti, Jayanti Chamling Rai
Alzheimer's disease (AD) is a heterogeneous neurodegenerative disorder and it is the most common form of dementia in the elderly. Early onset AD is caused by mutations in three genes: Amyloid-β precursor protein, presenilin 1 (PSEN1) and PSEN2. Late onset AD (LOAD) is complex and apolipoprotein E is the only unanimously accepted genetic risk factor for its development. Various genes implicated in AD have been identified using advanced genetic technologies, however, there are many additional genes that remain unidentified...
August 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28780366/transthyretin-neuroprotection-in-alzheimer-s-disease-is-dependent-on-proteolysis
#15
Catarina S Silva, Jessica Eira, Carlos A Ribeiro, Ângela Oliveira, Mónica M Sousa, Isabel Cardoso, Márcia A Liz
The deposition of amyloid β peptide (Aβ) in the hippocampus is one of the major hallmarks of Alzheimer's disease, a neurodegenerative disorder characterized by memory loss and cognitive impairment. The modulation of Aβ levels in the brain results from an equilibrium between its production from the amyloid precursor protein and removal by amyloid clearance proteins, which might occur via enzymatic (Aβ-degrading enzymes) or nonenzymatic (binding/transport proteins) reactions. Transthyretin (TTR) is one of the major Aβ-binding proteins acting as a neuroprotector in AD...
July 15, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28780149/synthesis-and-biological-evaluation-of-quinazolinone-based-hydrazones-with-potential-use-in-alzheimer-s-disease
#16
Zahra Haghighijoo, Omidreza Firuzi, Bahram Hemmateenejad, Saeed Emami, Najmeh Edraki, Ramin Miri
Discovering multifunctional agents for the treatment of Alzheimer's disease (AD) is an attractive therapeutic approach. BACE1 (β-site amyloid precursor protein cleaving enzyme 1) inhibitors may play a pivotal role in treating AD. Therefore, the discovery of novel non-peptide BACE1 inhibitors with desirable blood brain barrier permeability is a favorable approach for treatment. Moreover, the antioxidant potential of a drug could serve as an added value for designing dual-acting therapeutic agents. Here, we report the design, synthesis and biological evaluation of quinazolinone-hydrazone derivatives as new multi-target candidates for the treatment of AD...
July 25, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28776265/traumatic-brain-injury-alters-the-metabolism-and-facilitates-alzheimer-s-disease-in-a-murine-model
#17
Dandan Lou, Yao Du, Daochao Huang, Fang Cai, Yun Zhang, Tinyu Li, Weihui Zhou, Hongchang Gao, Weihong Song
A majority of Alzheimer's disease (AD) cases are sporadic without known cause. People who suffered from traumatic brain injury (TBI) are more likely to develop neurodegeneration and cognitive impairments. However, the role of TBI in pathophysiology of AD remains elusive. The present study intended to explore the effect of TBI on metabolism and its role in AD pathogenesis. We subjected double transgenic AD model mice APP23/PS45 to TBI. We found that TBI promoted β-secretase cleavage of amyloid β precursor protein and amyloid β protein deposition, and exuberated the cognitive impairments in AD mouse models...
August 3, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28776187/alzheimer-s-disease-related-amyloid-%C3%AE-1-42-peptide-induces-the-loss-of-human-sperm-function
#18
R S Tavares, S Martins, T Almeida-Santos, A P Sousa, J Ramalho-Santos, O A da Cruz E Silva
Characteristically identified as the main component of senile plaques present in patients suffering from Alzheimer's disease, Aβ has been detected in human testis and reproductive fluids, but its effect on spermatozoa has not been addressed. The present study evaluated whether the most toxic and aggregant amyloid precursor protein (APP)-proteolytic product, amyloid-β1-42 (Aβ1-42), was capable of affecting sperm functionality. Normozoospermic samples were either exposed to different Aβ1-42 doses or to the untreated and scrambled controls for a maximum of 48 h at 37 °C and 5%CO2, and motility, viability and mitochondrial status were evaluated...
August 3, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28774322/tau-accumulation-in-the-retina-promotes-early-neuronal-dysfunction-and-precedes-brain-pathology-in-a-mouse-model-of-alzheimer-s-disease
#19
Marius Chiasseu, Luis Alarcon-Martinez, Nicolas Belforte, Heberto Quintero, Florence Dotigny, Laurie Destroismaisons, Christine Vande Velde, Fany Panayi, Caroline Louis, Adriana Di Polo
BACKGROUND: Tau is an axon-enriched protein that binds to and stabilizes microtubules, and hence plays a crucial role in neuronal function. In Alzheimer's disease (AD), pathological tau accumulation correlates with cognitive decline. Substantial visual deficits are found in individuals affected by AD including a preferential loss of retinal ganglion cells (RGCs), the neurons that convey visual information from the retina to the brain. At present, however, the mechanisms that underlie vision changes in these patients are poorly understood...
August 3, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28770114/human-app-gene-expression-alters-active-zone-distribution-and-spontaneous-neurotransmitter-release-at-the-drosophila-larval-neuromuscular-junction
#20
Ekaterina A Saburova, Alexander N Vasiliev, Violetta V Kravtsova, Elena V Ryabova, Andrey L Zefirov, Olga I Bolshakova, Svetlana V Sarantseva, Igor I Krivoi
This study provides further insight into the molecular mechanisms that control neurotransmitter release. Experiments were performed on larval neuromuscular junctions of transgenic Drosophila melanogaster lines with different levels of human amyloid precursor protein (APP) production. To express human genes in motor neurons of Drosophila, the UAS-GAL4 system was used. Human APP gene expression increased the number of synaptic boutons per neuromuscular junction. The total number of active zones, detected by Bruchpilot protein puncta distribution, remained unchanged; however, the average number of active zones per bouton decreased...
2017: Neural Plasticity
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