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amyloid precursor protein

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https://www.readbyqxmd.com/read/29777753/characterization-of-impaired-cerebrovascular-structure-in-app-ps1-mouse-brains
#1
Kee-Chan Ahn, Cameron R Learman, Gary L Dunbar, Panchanan Maiti, Won-Cheoul Jang, Hyeon-Cheol Cha, Mee-Sook Song
Alzheimer's disease (AD) is defined by senile plaques, tauopathy and neuronal cell death in specific area of the brain. Recent studies suggest that neurovascular dysfunction may be an integral part of AD pathogenesis, contributing to the onset and development of AD pathologies such as neuronal death, inflammatory response, and breakdown of blood brain barrier (BBB). In addition, vascular complications caused by age-related metabolic diseases such as diabetes and high blood pressure have high incidence in development of dementia and AD...
May 16, 2018: Neuroscience
https://www.readbyqxmd.com/read/29777707/functional-analysis-of-juxta-and-intra-membrane-domains-of-murine-app-by-genome-editing-in-neuro2a-cells
#2
Nanaka Kaneshiro, Ryosuke Imaoka, Masato Komai, Taku Kashiyama, Takashi Sakurai, Takashi Uehara, Nobumasa Takasugi
Amyloid-β precursor protein (APP) correlates with the pathogenesis of certain brain diseases, such as Alzheimer disease (AD). APP is cleaved by several enzymes to produce APP metabolites, including the amyloid beta peptide (Aβ), which accumulates in the brain of AD patients. However, the exact functions of APP metabolites remain elusive. In this study, using genome editing technology, we mutated juxta- and intra-membrane domains of murine APP in the mouse neuroblastoma cell line, Neuro2a. We identified several clones that expressed characteristic patterns of APP metabolites...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775888/therapeutic-impact-of-rhuepo-on-abnormal-platelet-app-bace-1-presenilin-1-adam-10-and-a%C3%AE-expressions-in-chronic-kidney-disease-patients-with-cognitive-dysfunction-like-alzheimer-s-disease-a-pilot-study
#3
Vinothkumar G, Krishnakumar S, Sureshkumar, Shivashekar G, Sreedhar S, Preethikrishnan, Dinesh S, Sundaram A, Balakrishnan D, Riya, Venkataraman P
BACKGROUND: Cognitive dysfunction is reported to be a major cause of morbidity in chronic kidney disease (CKD). The senile plaques (SPs) in the brain are one of the most pathophysiological characteristics of cognitive dysfunction and its major constituent amyloid β (Aβ) released from amyloid precursor protein (APP) by β (BACE1) and γ (presenilin 1) secretases . Platelets contain more than 95% of the circulating APP and implicate as a candidate biomarker for cognitive decline. Recombinant human erythropoietin (rHuEPO) is a standard therapy for anemia in CKD and also acts as a neuroprotective agent...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775277/cid-9998128-compound-is-a-potential-multi-target-drug-for-alzheimer-s-disease
#4
Nguyen Quoc Thai, Zuzana Bednarikova, Miroslav Gancar, Huynh Quang Linh, Chin-Kun Hu, Mai Suan Li, Zuzana Gazova
We have probed capability of small CID 9998128 compound as a potential multi-target drug for the Alzheimer's disease (AD) using in silico and in vitro experiments. By all-atom simulation and MM-PBSA method we have demonstrated that this compound strongly binds to both amyloid beta 42 (Aβ42 ) fibrils and β-secretase and the van der Waals interaction is dominating over the electrostatic interaction in binding affinity. A detailed analysis at the atomic level revealed that indazole in CID 99998128 structure made a major contribution to instability of all studied complexes...
May 18, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29771527/protoilludane-illudalane-and-botryane-sesquiterpenoids-from-the-endophytic-fungus-phomopsis-sp-tj507a
#5
Shuangshuang Xie, Ye Wu, Yuben Qiao, Yi Guo, Jianping Wang, Zhengxi Hu, Qing Zhang, Xiaonian Li, Jinfeng Huang, Qun Zhou, Zengwei Luo, Junjun Liu, Hucheng Zhu, Yongbo Xue, Yonghui Zhang
To explore the chemical diversity of metabolites from endophytic fungi, the strain Phomopsis sp. TJ507A, isolated from the medicinal plant Phyllanthus glaucus, was investigated. A 2,3- seco-protoilludane-type sesquiterpenoid (1), eight protoilludane-type sesquiterpenoids (2-9), four illudalane-type sesquiterpenoids (10a/10b, 11, and 12), and a botryane-type sesquiterpenoid (13) in addition to seven known sesquiterpenoids (14-20) were identified from the liquid culture of the fungus. Structures of the isolated compounds, including their absolute configurations, were elucidated based on extensive spectroscopic analyses, a modified Mosher analysis, electronic circular dichroism (ECD) calculations, and [Rh2 (OCOCF3 )4 ]-induced ECD spectra as well as X-ray crystallographic analyses...
May 17, 2018: Journal of Natural Products
https://www.readbyqxmd.com/read/29768974/brain-phospholipid-precursors-administered-post-injury-reduce-tissue-damage-and-improve-neurological-outcome-in-experimental-traumatic-brain-injury
#6
Orli Thau-Zuchman, Rita Noutel Gomes, Simon Christopher Dyall, Meirion Davis, John V Priestley, Martine Groenendijk, Martijn DE Wilde, Jordi Lopez-Tremoleda, Adina T Michael-Titus
Traumatic brain injury (TBI) leads to cellular loss, destabilisation of membranes, disruption of synapses and altered brain connectivity, and increased risk of neurodegenerative disease. A significant and long-lasting decrease in phospholipids (PL), essential membrane constituents, has recently been reported in plasma and brain tissue, in human and experimental TBI. We hypothesised that supporting PL synthesis post-injury could improve outcome after TBI. We tested this hypothesis using a multi-nutrient combination designed to support the biosynthesis of phospholipids and available for clinical use...
May 17, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29768194/extracellular-forms-of-a%C3%AE-and-tau-from-ipsc-models-of-alzheimer-s-disease-disrupt-synaptic-plasticity
#7
Neng-Wei Hu, Grant T Corbett, Steven Moore, Igor Klyubin, Tiernan T O'Malley, Dominic M Walsh, Frederick J Livesey, Michael J Rowan
The early stages of Alzheimer's disease are associated with synaptic dysfunction prior to overt loss of neurons. To identify extracellular molecules that impair synaptic plasticity in the brain, we studied the secretomes of human iPSC-derived neuronal models of Alzheimer's disease. When introduced into the rat brain, secretomes from human neurons with either a presenilin-1 mutation, amyloid precursor protein duplication, or trisomy of chromosome 21 all strongly inhibit hippocampal long-term potentiation. Synaptic dysfunction caused by presenilin-1 mutant and amyloid precusor protein duplication secretomes is mediated by Aβ peptides, whereas trisomy of chromosome 21 (trisomy 21) neuronal secretomes induce dysfunction through extracellular tau...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29763304/synthesis-structure-activity-relationships-and-preclinical-evaluation-of-heteroaromatic-amides-and-1-3-4-oxadiazole-derivatives-as-5-ht4-receptor-partial-agonists
#8
Ramakrishna Nirogi, Abdul Rasheed Mohammed, Anil K Shinde, Shankar Reddy Gagginapally, Durga Malleshwari Kancharla, Vanaja Reddy Middekadi, Narsimha Bogaraju, Srinivasa Rao Ravella, Pooja Singh, Sumit Raosaheb Birangal, Ramkumar Subramanian, Raghava Choudary Palacharla, Vijay Benade, Nageswararao Muddana, Pradeep Jayarajan
Alzheimer's disease (AD) is a neurodegenerative disorder which has a higher prevalence and incidence in people older than 60 years. The need for improved AD therapies is unmet as the current therapies are symptomatic with modest efficacy. The 5-HT4 receptor (5-HT4R) partial agonists offer both symptomatic and disease modifying treatment as they shift amyloid precursor protein (APP) processing from amyloidogenic to non-amyloidogenic pathway by activating α-secretase enzyme. In addition, they also offer symptomatic treatment by increasing neurotransmitter acetylcholine levels in the brain...
May 15, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29760662/targeting-renin-angiotensin-system-against-alzheimer-s-disease
#9
REVIEW
Abadi Kahsu Gebre, Birhanetensay Masresha Altaye, Tesfay Mehari Atey, Kald Beshir Tuem, Derbew Fikadu Berhe
Renin Angiotensin System (RAS) is a hormonal system that regulates blood pressure and fluid balance through a coordinated action of renal, cardiovascular, and central nervous systems. In addition to its hemodynamic regulatory role, RAS involves in many brain activities, including memory acquisition and consolidation. This review has summarized the involvement of RAS in the pathology of Alzheimer's disease (AD), and the outcomes of treatment with RAS inhibitors. We have discussed the effect of brain RAS in the amyloid plaque (Aβ) deposition, oxidative stress, neuroinflammation, and vascular pathology which are directly and indirectly associated with AD...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29752653/imaging-neurodegeneration-in-down-syndrome-brain-templates-for-amyloid-burden-and-tissue-segmentation
#10
Patrick J Lao, Ben L Handen, Tobey J Betthauser, Karly A Cody, Annie D Cohen, Dana L Tudorascu, Charles K Stone, Julie C Price, Sterling C Johnson, William E Klunk, Bradley T Christian
The focus of Alzheimer's disease (AD) neuroimaging research has shifted towards an investigation of the earliest stages of AD pathogenesis, which manifests in every young adult with Down syndrome (DS; trisomy 21) resulting from a deterministic genetic predisposition to amyloid precursor protein overproduction. Due to morphological differences in brain structure in the DS population, special consideration must be given to processing pipelines and the use of normative atlases developed for the non-DS population...
May 11, 2018: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/29744845/disaggregation-of-a%C3%AE-42-for-structural-and-biochemical-studies
#11
Hyewon Chung, Elliot J Crooks, Martine Ziliox, Steven O Smith
The amyloid-β (Aβ) peptides that form the amyloid fibrils associated with Alzheimer's disease are generated by sequential proteolysis of the amyloid precursor protein by β- and γ-secretase. The two predominant Aβ peptides, Aβ40 and Aβ42, differ by two amino acids, are soluble as monomers at low concentration (and/or low temperature) and are normally cleared from the brain parenchyma. In order to study the structure and assembly of these peptides, they are often synthesized using solid-phase peptide synthesis and purified...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29743204/apoe-isoforms-and-carboxyl-terminal-truncated-apoe4-forms-affect-neuronal-bace1-levels-and-a%C3%AE-production-independently-of-their-cholesterol-efflux-capacity
#12
Ioannis Dafnis, Christina Raftopoulou, Christina Mountaki, Evgenia Megalou, Vassilis I Zannis, Angeliki Chroni
The beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) initiates the production of amyloid-beta peptide (Aβ) which is central to the pathogenesis of Alzheimer's disease (AD). Changes in brain cholesterol homeostasis have been suggested to affect Aβ metabolism. Cholesterol homeostasis is maintained in the brain by apolipoprotein E (apoE). The apoE4 isoform constitutes the major risk factor for AD. Here, we investigated the effect of apoE forms on Aβ generation and on BACE1 levels. We also examined the potential involvement in these processes of cholesterol transporters ABCG1 and ABCG4 or the lipoprotein receptor SR-BI that are implicated in cholesterol efflux to apoE...
May 9, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29741097/metabolic-and-structural-imaging-at-7-tesla-after-repetitive-mild-traumatic-brain-injury-in-immature-rats
#13
Emin Fidan, Lesley M Foley, Lee Ann New, Henry Alexander, Patrick M Kochanek, T Kevin Hitchens, Hülya Bayır
Mild traumatic brain injury (mTBI) in children is a common and serious public health problem. Traditional neuroimaging findings in children who sustain mTBI are often normal, putting them at risk for repeated mTBI (rmTBI). There is a need for more sensitive imaging techniques capable of detecting subtle neurophysiological alterations after injury. We examined neurochemical and white matter changes using diffusion tensor imaging of the whole brain and proton magnetic resonance spectroscopy of the hippocampi at 7 Tesla in 18-day-old male rats at 7 days after mTBI and rmTBI...
January 2018: ASN Neuro
https://www.readbyqxmd.com/read/29740285/ovarian-function-modulates-the-effects-of-long-chain-polyunsaturated-fatty-acids-on-the-mouse-cerebral-cortex
#14
Jose L Herrera, Lara Ordoñez-Gutierrez, Gemma Fabrias, Josefina Casas, Araceli Morales, Guadalberto Hernandez, Nieves G Acosta, Covadonga Rodriguez, Luis Prieto-Valiente, Luis M Garcia-Segura, Rafael Alonso, Francisco G Wandosell
Different dietary ratios of n -6/ n -3 long-chain polyunsaturated fatty acids (LC-PUFAs) may alter brain lipid profile, neural activity, and brain cognitive function. To determine whether ovarian hormones influence the effect of diet on the brain, ovariectomized and sham-operated mice continuously treated with placebo or estradiol were fed for 3 months with diets containing low or high n -6/ n -3 LC-PUFA ratios. The fatty acid (FA) profile and expression of key neuronal proteins were analyzed in the cerebral cortex, with intact female mice on standard diet serving as internal controls of brain lipidome composition...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29739836/inhibition-of-pkc%C3%AE-reduces-amyloid-%C3%AE-levels-and-reverses-alzheimer-disease-phenotypes
#15
Ying Du, Yingjun Zhao, Chuan Li, Qiuyang Zheng, Jing Tian, Zhuyi Li, Timothy Y Huang, Wei Zhang, Huaxi Xu
β-amyloid protein (Aβ) plays a central role in the pathogenesis of Alzheimer disease (AD). Aβ is generated from sequential cleavage of amyloid precursor protein (APP) by β-site APP-cleaving enzyme 1 (BACE1) and the γ-secretase complex. Although activation of some protein kinase C (PKC) isoforms such as PKCα and ε has been shown to regulate nonamyloidogenic pathways and Aβ degradation, it is unclear whether other PKC isoforms are involved in APP processing/AD pathogenesis. In this study, we report that increased PKCδ levels correlate with BACE1 expression in the AD brain...
May 8, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29737327/interference-of-citrate-stabilized-gold-nanoparticles-with-%C3%AE-2-microglobulin-oligomeric-association
#16
Cristina Cantarutti, Gijo Raj, Federico Fogolari, Sofia Giorgetti, Alessandra Corazza, Vittorio Bellotti, Panče Naumov, Gennaro Esposito
Protein fibrillation is involved in many serious diseases, and protein oligomers are proved to be precursors of amyloid fibrils. NMR and QCMD experiments allowed us to establish that the interaction between citrate-stabilized gold nanoparticles and a paradigmatic amyloidogenic protein, β2-microglobulin, is able to interfere with protein association into oligomers.
May 8, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29733887/the-interactions-of-p53-with-tau-and-a%C3%A3-represent-potential-therapeutic-targets-for-alzheimer-s-disease
#17
REVIEW
Maja Jazvinšćak Jembrek, Neda Slade, Patrick R Hof, Goran Šimić
Alzheimer's disease (AD), the most common progressive neurodegenerative disorder, is characterized by severe cognitive decline and personality changes as a result of synaptic and neuronal loss. The defining clinicopathological hallmarks of the disease are deposits of amyloid precursor protein (APP)-derived amyloid-β peptides (Aβ) in the brain parenchyma, and intracellular aggregates of truncated and hyperphosphorylated tau protein in neurofibrillary tangles (NFT). At the cellular and molecular levels, many intertwined pathological mechanisms that relate Aβ and tau pathology with a transcription factor p53 have been revealed...
May 4, 2018: Progress in Neurobiology
https://www.readbyqxmd.com/read/29729742/inkjet-printing-based-%C3%AE-secretase-fluorescence-resonance-energy-transfer-fret-assay-for-screening-of-potential-%C3%AE-secretase-inhibitors-of-alzheimer-s-disease
#18
Jungmi Lee, Annie Agnes Suganya Samson, Joon Myong Song
Amyloid-β (Aβ) is generated by proteolytic processing of amyloid precursor protein (APP) by beta-secretase (BACE-1) and gamma-secretase. Amyloid-β is responsible for the formation of senile plaques in Alzheimer's disease (AD). Consequently, inhibition of β-secretase (BACE-1), a rate-limiting enzyme in the production of Aβ, constitutes an attractive therapeutic approach to the treatment of AD. This paper reports an inkjet printing-based fluorescence assay for high throughput screening of β-secretase inhibitors achieved by employing a BACE-1 FRET substrate (Rh-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-Lys-Quencher)...
August 31, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29729668/urmc-099-facilitates-amyloid-%C3%AE-clearance-in-a-murine-model-of-alzheimer-s-disease
#19
Tomomi Kiyota, Jatin Machhi, Yaman Lu, Bhagyalaxmi Dyavarshetty, Maryam Nemati, Gang Zhang, R Lee Mosley, Harris A Gelbard, Howard E Gendelman
BACKGROUND: The mixed lineage kinase type 3 inhibitor URMC-099 facilitates amyloid-beta (Aβ) clearance and degradation in cultured murine microglia. One putative mechanism is an effect of URMC-099 on Aβ uptake and degradation. As URMC-099 promotes endolysosomal protein trafficking and reduces Aβ microglial pro-inflammatory activities, we assessed whether these responses affect Aβ pathobiogenesis. To this end, URMC-099's therapeutic potential, in Aβ precursor protein/presenilin-1 (APP/PS1) double-transgenic mice, was investigated in this model of Alzheimer's disease (AD)...
May 5, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29729423/interaction-between-a-mapt-variant-causing-frontotemporal-dementia-and-mutant-app-affects-axonal-transport
#20
Robert Adalbert, Stefan Milde, Claire Durrant, Kunie Ando, Virginie Stygelbout, Zehra Yilmaz, Stacey Gould, Jean-Pierre Brion, Michael P Coleman
In Alzheimer's disease, many indicators point to a central role for poor axonal transport, but the potential for stimulating axonal transport to alleviate the disease remains largely untested. Previously, we reported enhanced anterograde axonal transport of mitochondria in 8- to 11-month-old MAPTP301L knockin mice, a genetic model of frontotemporal dementia with parkinsonism-17T. In this study, we further characterized the axonal transport of mitochondria in younger MAPTP301L mice crossed with the familial Alzheimer's disease model, TgCRND8, aiming to test whether boosting axonal transport in young TgCRND8 mice can alleviate axonal swelling...
April 5, 2018: Neurobiology of Aging
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