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amyloid precursor protein

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https://www.readbyqxmd.com/read/27921243/comparison-of-rnai-ngr-and-nep1-40-in-acting-on-axonal-regeneration-after-spinal-cord-injury-in-rat-models
#1
Jing Xu, Jian He, Huang He, Renjun Peng, Jian Xi
This study was intended to compare the therapeutic efficacies of NEP1-40 and SiNgR199 on treating spinal cord injury (SCI). Nogo-A, growth associated protein 43 (GAP-43), microtubule associated protein 2 (MAP-2), and amyloid βA4 precursor protein (APP) expressions were determined using western blot and quantitative PCR. Neurite outgrowth detected the growth of neurites, and BDA anterograde tracing was used to label the regenerated axonal. Rats' behavior was assessed with Basso, Beattie, and Bresnahan locomotor rating scale (BBB)...
December 5, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27918287/measuring-discrimination-and-reversal-learning-in-mouse-models-within-4-days-and-without-prior-food-deprivation
#2
Esther Remmelink, August B Smit, Matthijs Verhage, Maarten Loos
Many neurological and psychiatric disorders are characterized by deficits in cognitive flexibility. Modeling cognitive flexibility in mice enables the investigation of mechanisms underlying these deficits. The majority of currently available behavioral tests targeting this cognitive domain are reversal learning tasks that require scheduled food restriction, extended training periods and labor-intensive, and stress-inducing animal handling. Here, we describe a novel 4-day (4-d) continuously running task measuring discrimination- and reversal learning in an automated home cage (CognitionWall DL/RL task) that largely eliminates these limitations...
November 2016: Learning & Memory
https://www.readbyqxmd.com/read/27917122/glucagon-like-peptide-1-analog-liraglutide-delays-onset-of-experimental-autoimmune-encephalitis-in-lewis-rats
#3
Brian DellaValle, Gitte S Brix, Birgitte Brock, Michael Gejl, Anne M Landau, Arne Møller, Jørgen Rungby, Agnete Larsen
Introduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS) pathology and influence the susceptibility to treatment, directing attention toward anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1) family, is also anti-diabetic and weight-reducing and is, moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE)...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27911326/localization-and-processing-of%C3%A2-the%C3%A2-amyloid-%C3%AE-protein-precursor-in%C3%A2-mitochondria-associated-membranes
#4
Dolores Del Prete, Jan M Suski, Bénédicte Oulès, Delphine Debayle, Anne Sophie Gay, Sandra Lacas-Gervais, Renaud Bussiere, Charlotte Bauer, Paolo Pinton, Patrizia Paterlini-Bréchot, Mariusz R Wieckowski, Frédéric Checler, Mounia Chami
Alteration of mitochondria-associated membranes (MAMs) has been proposed to contribute to the pathogenesis of Alzheimer's disease (AD). We studied herein the subcellular distribution, the processing, and the protein interactome of the amyloid-β protein precursor (AβPP) and its proteolytic products in MAMs. We reveal that AβPP and its catabolites are present in MAMs in cellular models overexpressing wild type AβPP or AβPP harboring the double Swedish or London familial AD mutations, and in brains of transgenic mice model of AD...
November 26, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911305/nitrosylation-of-vesicular-transporters-in-brain-of-amyloid-precursor-protein-presenilin-1-double-transgenic-mice
#5
Ying Wang, Zhu Zhou, Hua Tan, Shenghua Zhu, Yiran Wang, Yingxia Sun, Xin-Min Li, Jun-Feng Wang
Nitric oxide can attack thiol groups of cysteine residues in proteins and induce protein cysteine S-nitrosylation. Cholinergic and glutamatergic systems are dysregulated in Alzheimer's disease. Vesicular acetylcholine transporter (VAChT) and vesicular glutamate transporter 1 (VGLUT1) are important in packaging acetylcholine and glutamate into vesicles, which is an important step for neurotransmission. Previously we found that VAChT and VGLUT1 can be nitrosylated and that S-nitrosylation of these transporters inhibits vesicular uptake of acetylcholine and glutamate...
November 26, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911303/amylin-treatment-reduces-neuroinflammation-and-ameliorates-abnormal-patterns-of-gene-expression-in%C3%A2-the-cerebral-cortex-of-an-alzheimer-s-disease-mouse-model
#6
Erming Wang, Haihao Zhu, Xiaofan Wang, Adam Gower, Max Wallack, Jan Krzysztof Blusztajn, Neil Kowall, Wei Qiao Qiu
Our recent study has demonstrated that peripheral amylin treatment reduces the amyloid pathology in the brain of Alzheimer's disease (AD) mouse models, and improves their learning and memory. We hypothesized that the beneficial effects of amylin for AD was beyond reducing the amyloids in the brain, and have now directly tested the actions of amylin on other aspects of AD pathogenesis, especially neuroinflammation. A 10-week course of peripheral amylin treatment significantly reduced levels of cerebral inflammation markers, Cd68 and Iba1, in amyloid precursor protein (APP) transgenic mice...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27908798/platelets-are-responsible-for-the-accumulation-of-%C3%AE-amyloid-in-blood-clots-inside-and-around-blood-vessels-in-mouse-brain-after-thrombosis
#7
Lilia Y Kucheryavykh, Josué Dávila-Rodríguez, David E Rivera-Aponte, Lidia V Zueva, A Valance Washington, Priscilla Sanabria, Mikhail Y Inyushin
INTRODUCTION: Platelets contain beta-amyloid precursor protein (APP) as well as Aβ peptide (Aβ) that can be released upon activation. During thrombosis, platelets are concentrated in clots and activated. METHODS: We used in vivo fluorescent analysis and electron microscopy in mice to determine to what degree platelets are concentrated in clots. We used immunostaining to visualize Aβ after photothrombosis in mouse brains. RESULTS: Both in vivo results and electron microscopy revealed that platelets were 300-500 times more concentrated in clots than in non-clotted blood...
November 28, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27908425/copper-accumulation-in-rodent-brain-astrocytes-a-species-difference
#8
Brendan Sullivan, Gregory Robison, Yulia Pushkar, John K Young, Kebreten F Manaye
Changes in Cu homeostasis have been implicated in multiple neurodegenerative diseases. Factors controlling and regulating the distribution of Cu in the brain remain largely unknown. We have previously reported that a sub-set of astrocytes in the subventricular zone (SVZ) contain Cu-rich aggregates. Here we expand previous studies with detailed X-ray fluorescent imaging (XRF) analysis of the additional brain areas of hippocampus (HP) and rostral migratory stream (RMS). We also use conventional DAB (3,3'-diaminobenzidine) staining which accesses both peroxidase and pseudo-peroxidase activities...
January 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27908423/copper-brain-protein-protection-against-free-radical-induced-neuronal-death-survival-ratio-in-sh-sy5y-neuroblastoma-cell-cultures
#9
Roger Deloncle, Bernard Fauconneau, Olivier Guillard, José Delaval, Gérard Lesage, Alain Pineau
In Creutzfeldt Jakob, Alzheimer and Parkinson diseases, copper metalloproteins such as prion, amyloid protein precursor and α-synuclein are able to protect against free radicals by reduction from cupric Cu(+2) to cupreous Cu(+). In these pathologies, a regional copper (Cu) brain decrease correlated with an iron, zinc or manganese (Mn) increase has previously been observed, leading to local neuronal death and abnormal deposition of these metalloproteins in β-sheet structures. In this study we demonstrate the protective effect of Cu metalloproteins against deleterious free-radical effects...
January 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27906174/therapeutic-advantage-of-pro-electrophilic-drugs-to-activate-the-nrf2-are-pathway-in-alzheimer-s-disease-models
#10
Stuart A Lipton, Tayebeh Rezaie, Anthony Nutter, Kevin M Lopez, James Parker, Kunio Kosaka, Takumi Satoh, Scott R McKercher, Eliezer Masliah, Nobuki Nakanishi
Alzheimer's disease (AD) is characterized by synaptic and neuronal loss, which occurs at least partially through oxidative stress induced by oligomeric amyloid-β (Aβ)-peptide. Carnosic acid (CA), a chemical found in rosemary and sage, is a pro-electrophilic compound that is converted to its active form by oxidative stress. The active form stimulates the Keap1/Nrf2 transcriptional pathway and thus production of phase 2 antioxidant enzymes. We used both in vitro and in vivo models. For in vitro studies, we evaluated protective effects of CA on primary neurons exposed to oligomeric Aβ...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27904493/beta-2-adrenergic-receptor-activation-enhances-neurogenesis-in-alzheimer-s-disease-mice
#11
Gao-Shang Chai, Yang-Yang Wang, Amina Yasheng, Peng Zhao
Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer's disease. Enhancing adult hippocampal neurogenesis has been pursued as a potential therapeutic strategy for Alzheimer's disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer's disease...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27902765/loss-of-cathepsin-b-and-l-leads-to-lysosomal-dysfunction-npc-like-cholesterol-sequestration-and-accumulation-of-the-key-alzheimer-s-proteins
#12
Stjepko Cermak, Marko Kosicek, Aleksandra Mladenovic-Djordjevic, Kosara Smiljanic, Selma Kanazir, Silva Hecimovic
Proper function of lysosomes is particularly important in neurons, as they cannot dilute accumulated toxic molecules and aggregates by cell division. Thus, impairment of lysosomal function plays an important role in neuronal degeneration and in the pathogenesis of numerous neurodegenerative diseases. In this work we analyzed how inhibition and/or loss of the major lysosomal proteases, the cysteine cathepsins B and L (CtsB/L), affects lysosomal function, cholesterol metabolism and degradation of the key Alzheimer's disease (AD) proteins...
2016: PloS One
https://www.readbyqxmd.com/read/27900617/new-and-evolving-concepts-regarding-the-prognosis-and-treatment-of-cardiac-amyloidosis
#13
REVIEW
Stefano Perlini, Roberta Mussinelli, Francesco Salinaro
Systemic amyloidoses are rare and proteiform diseases, caused by extracellular accumulation of insoluble misfolded fibrillar proteins. Prognosis is dictated by cardiac involvement, which is especially frequent in light chain (AL) and in transthyretin variants (ATTR, both mutated, (ATTRm), and wild-type, (ATTRwt)). Recently, ATTRwt has emerged as a potentially relevant cause of a heart failure with preserved ejection fraction (HFpEF). Cardiac amyloidosis is an archetypal example of restrictive cardiomyopathy, with signs and symptoms of global heart failure and diastolic dysfunction...
November 29, 2016: Current Heart Failure Reports
https://www.readbyqxmd.com/read/27894840/overexpression-of-mterf4-promotes-the-amyloidogenic-processing-of-app-by-inhibiting-adam10
#14
Xiao-Liang Wang, Qing Liu, Guo-Jun Chen, Mei-Ling Li, Yan-Hui Ding
Alzheimer's disease (AD) is characterized by the deposition of β-amyloid (Aβ) peptide in the brain, which is produced by the proteolysis of β-amyloid precursor protein (APP). Recently, the mitochondrial transcription factor 4 (MTERF4), a member of the MTERF family, was implicated in regulating mitochondrial DNA transcription and directly in controlling mitochondrial ribosomal translation. The present study identified a novel role for MTERF4 in shifting APP processing toward the amyloidogenic pathway. The levels of MTERF4 protein were significantly increased in the hippocampus of APP/PS1 mice...
November 25, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27891669/a-molecular-dynamics-study-of-the-binary-complexes-of-app-jip1-and-the-cargo-binding-domain-of-klc
#15
Cooper A Taylor, Bill R Miller, Soleil S Shah, Carol A Parish
Mutations in the amyloid precursor protein (APP) are responsible for the formation of amyloid-β peptides. These peptides play a role in Alzheimer's and other dementia-related diseases. The cargo binding domain of the kinesin-1 light chain motor protein (KLC1) may be responsible for transporting APP either directly or via interaction with C-jun N-terminal kinase-interacting protein 1 (JIP1). However, to date there has been no direct experimental or computational assessment of such binding at the atomistic level...
November 7, 2016: Proteins
https://www.readbyqxmd.com/read/27891075/bace1-rnai-restores-the-composition-of-phosphatidylethanolamine-derivates-related-to-memory-improvement-in-aged-3xtg-ad-mice
#16
Javier G Villamil-Ortiz, Alvaro Barrera-Ocampo, Diego Piedrahita, Claudia M Velásquez-Rodríguez, Julian D Arias-Londoño, Gloria P Cardona-Gómez
β-amyloid (Aβ) is produced by the β-secretase 1 (BACE1)-mediated enzymatic cleavage of the amyloid precursor protein through the amyloidogenic pathway, making BACE1 a therapeutic target against Alzheimer's disease (AD). Alterations in lipid metabolism are a risk factor for AD by an unknown mechanism. The objective of this study was to determine the effect of RNA interference against BACE1 (shBACEmiR) on the phospholipid profile in hippocampal CA1 area in aged 3xTg-AD mice after 6 and 12 months of treatment compared to aged PS1KI mice...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27889678/early-hippocampal-hyperexcitability-in-ps2app-mice-role-of-mutant-ps2-and-app
#17
Roberto Fontana, Mario Agostini, Emanuele Murana, Mufti Mahmud, Elena Scremin, Maria Rubega, Giovanni Sparacino, Stefano Vassanelli, Cristina Fasolato
Alterations of brain network activity are observable in Alzheimer's disease (AD) together with the occurrence of mild cognitive impairment, before overt pathology. However, in humans as well in AD mouse models, identification of early biomarkers of network dysfunction is still at its beginning. We performed in vivo recordings of local field potential activity in the dentate gyrus of PS2APP mice expressing the human amyloid precursor protein (APP) Swedish mutation and the presenilin-2 (PS2) N141I. From a frequency-domain analysis, we uncovered network hyper-synchronicity as early as 3 months, when intracellular accumulation of amyloid beta was also observable...
November 5, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/27889467/treadmill-exercise-decreases-amyloid-%C3%AE-burden-possibly-via-activation-of-sirt-1-signaling-in-a-mouse-model-of-alzheimer-s-disease
#18
Jung-Hoon Koo, Eun-Bum Kang, Yoo-Sung Oh, Dae-Seung Yang, Joon-Yong Cho
Accumulation of amyloid-β (Aβ) correlates significantly with progressive cognitive deficits, a main symptom of Alzheimer's disease (AD). Although treadmill exercise reduces Aβ levels, the molecular mechanisms underlying the effects are not fully understood. We hypothesize that treadmill exercise decreases Aβ production and alleviates cognitive deficits by activating the non-amyloidogenic pathway via SIRT-1 signaling. Treadmill exercise improved cognitive deficits and alleviated neurotoxicity. Most importantly, treadmill exercise increased SIRT-1 level, which subsequently resulted in increased ADAM-10 level by down-regulation of ROCK-1 and upregulation of RARβ, ultimately facilitating the non-amyloidogenic pathway...
November 23, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27884064/amyloid-fibril-proteins-and-amyloidosis-chemical-identification-and-clinical-classification-international-society-of-amyloidosis-2016-nomenclature-guidelines
#19
Jean D Sipe, Merrill D Benson, Joel N Buxbaum, Shu-Ichi Ikeda, Giampaolo Merlini, Maria J M Saraiva, Per Westermark
The Nomenclature Committee of the International Society of Amyloidosis (ISA) met during the XVth Symposium of the Society, 3 July-7 July 2016, Uppsala, Sweden, to assess and formulate recommendations for nomenclature for amyloid fibril proteins and the clinical classification of the amyloidoses. An amyloid fibril must exhibit affinity for Congo red and with green, yellow or orange birefringence when the Congo red-stained deposits are viewed with polarized light. While congophilia and birefringence remain the gold standard for demonstration of amyloid deposits, new staining and imaging techniques are proving useful...
December 2016: Amyloid: the International Journal of Experimental and Clinical Investigation
https://www.readbyqxmd.com/read/27883916/hydrogen-sulfide-ameliorates-learning-memory-impairment-in-app-ps1-transgenic-mice-a-novel-mechanism-mediated-by-the-activation-of-nrf2
#20
Yuangui Liu, Yuanyuan Deng, Huiyu Liu, Caixia Yin, Xiaohui Li, Qihai Gong
Beta-amyloid (Aβ) plaques and oxidative stress are associated with the pathogenesis of Alzheimer's disease (AD). Hydrogen sulfide (H2S) has been recognized as a cytoprotectant, which improves learning memory impairment and exerts antioxidant effects in neurodegenerative disorders, including AD. The experiment was projected to explore the effects of H2S on cognitive deficits, Aβ levels and possible antioxidant mechanisms. Here, APP/PS1 transgenic mice were injected sodium hydrosulfide (NaHS, a H2S donor, 2...
November 21, 2016: Pharmacology, Biochemistry, and Behavior
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