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amyloid precursor protein

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https://www.readbyqxmd.com/read/28103298/perinatal-choline-supplementation-reduces-amyloidosis-and-increases-choline-acetyltransferase-expression-in-the-hippocampus-of-the-appsweps1de9-alzheimer-s-disease-model-mice
#1
Tiffany J Mellott, Olivia M Huleatt, Bethany N Shade, Sarah M Pender, Yi B Liu, Barbara E Slack, Jan K Blusztajn
Prevention of Alzheimer's disease (AD) is a major goal of biomedical sciences. In previous studies we showed that high intake of the essential nutrient, choline, during gestation prevented age-related memory decline in a rat model. In this study we investigated the effects of a similar treatment on AD-related phenotypes in a mouse model of AD. We crossed wild type (WT) female mice with hemizygous APPswe/PS1dE9 (APP.PS1) AD model male mice and maintained the pregnant and lactating dams on a control AIN76A diet containing 1...
2017: PloS One
https://www.readbyqxmd.com/read/28102934/crosstalk-between-angiotensin-and-the-non-amyloidogenic-pathway-of-alzheimer-s-amyloid-precursor-protein
#2
Anna Maria Kanarek, Annika Wagner, Jim Küppers, Michael Gütschow, Rolf Postina, Elzbieta Kojro
The association between hypertension and an increased risk for Alzheimer's disease (AD) and dementia is well established. Many data suggest that modulation of the renin-angiotensin system may be meaningful for the prevention and therapy of neurodegenerative disorders, in particular AD. Proteolytic cleavage of the amyloid precursor protein (APP) by α-secretase precludes formation of neurotoxic Aβ peptides and is expected to counteract the development of AD. An established approach for the up-regulation of α-secretase cleavage is activation of G protein-coupled receptors (GPCRs)...
January 19, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28102781/a-neurodevelopmental-disorder-with-a-nonsense-mutation-in-the-ox-2-antigen-domain-of-the-amyloid-precursor-protein-app-gene
#3
Khue Vu Nguyen, Karen Leydiker, Raymond Wang, Jose Abdenur, William L Nyhan
We report a patient, an infant with a neurodevelopmental disorder manifesting intractable complex partial epilepsy, bull's eye maculopathy, microcephaly, bilateral cataracts, truncal hypotonia, and spasticity of all four extremities. Sequencing of genomic DNA revealed mutations in (a) exon 8 (Ox-2 antigen domain) of the amyloid precursor protein (APP) gene: c.1075C>T, p.Arg359(*) (b) exon 8 of the senataxin (SETX) gene: c.4738C>T, p.Arg1580Cys, and (c) exon 2 of the ceroid-lipofuscinosis, neuronal 8 (CLN8) gene: c...
January 19, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28099462/acute-and-chronic-sustained-hypoxia-do-not-substantially-regulate-amyloid-%C3%AE-peptide-generation-in-vivo
#4
Alberto Serrano-Pozo, Manuel A Sánchez-García, Antonio Heras-Garvín, Rosana March-Díaz, Victoria Navarro, Marisa Vizuete, José López-Barneo, Javier Vitorica, Alberto Pascual
BACKGROUND: Recent epidemiological evidence has linked hypoxia with the development of Alzheimer disease (AD). A number of in vitro and in vivo studies have reported that hypoxia can induce amyloid-β peptide accumulation through various molecular mechanisms including the up-regulation of the amyloid-β precursor protein, the β-secretase Bace1, or the γγ-secretase complex components, as well as the down-regulation of Aβ-degrading enzymes. OBJECTIVES: To investigate the effects of acute and chronic sustained hypoxia in Aβ generation in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28098506/capsicum-annuum-var-grossum-bell-pepper-inhibits-%C3%AE-secretase-activity-and-%C3%AE-amyloid1-40-aggregation
#5
Omodesola Oluwafisayo Ogunruku, Ganiyu Oboh, Sabina Passamonti, Federica Trammer, Aline Augusti Boligon
The deposition of amyloid protein as senile plaques is the major signature of Alzheimer's disease (AD). It is produced by the sequential cleavage of the amyloid precursor protein by secretases. Moreover, peppers are noted for their antiaging and cognitive enhancing properties. Thus, in this study, the effects of polyphenol-rich extracts from bell pepper on amyloid production and aggregation in vitro were investigated. Bell pepper (ripe and unripe) was extracted with methanol-1 N HCl (1:1 v/v). Thereafter, the inhibitory potentials of the extracts on β-secretase and β-amyloid1-40 aggregation were determined...
January 18, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28096459/zinc-and-copper-differentially-modulate-amyloid-precursor-protein-processing-by-%C3%AE-secretase-and-amyloid-%C3%AE-peptide-production
#6
Hermeto Gerber, Fang Wu, Mitko Dimitrov, Guillermo M Garcia Osuna, Patrick C Fraering
Recent evidence suggests involvement of biometal homeostasis in the pathological mechanisms in Alzheimer's disease (AD). For example, increased intracellular copper or zinc has been linked to a reduction in secreted levels of the AD-causing amyloid-β peptide (Aβ). However, little is known about whether these biometals modulate the generation of Aβ. In the present study, we demonstrate in both cell-free and cell-based assays that zinc and copper regulate Aβ production by distinct molecular mechanisms affecting the processing by γ-secretase of its Aβ precursor protein substrate APP-C99...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28093699/anti-alzheimer-s-disease-activity-of-compounds-from-the-root-bark-of-morus-alba-l
#7
Eun Bi Kuk, A Ra Jo, Seo In Oh, Hee Sook Sohn, Su Hui Seong, Anupom Roy, Jae Sue Choi, Hyun Ah Jung
The inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) plays important roles in prevention and treatment of Alzheimer's disease (AD). Among the individual parts of Morus alba L. including root bark, branches, leaves, and fruits, the root bark showed the most potent enzyme inhibitory activities. Therefore, the aim of this study was to evaluate the anti-AD activity of the M. alba root bark and its isolate compounds, including mulberrofuran G (1), albanol B (2), and kuwanon G (3) via inhibition of AChE, BChE, and BACE1...
January 16, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28091531/tnf-%C3%AE-regulates-the-proteolytic-degradation-of-st6gal-1-and-endothelial-cell-cell-junctions-through-upregulating-expression-of-bace1
#8
Xiao Deng, Jun Zhang, Yan Liu, Linmu Chen, Chao Yu
Endothelial dysfunction and monocyte adhesion to vascular endothelial cells are two critical steps in atherosclerosis development, and emerging evidence suggests that protein sialylation is involved in these processes. However, the mechanism underlying this phenomenon remains incompletely elucidated. In this study, we demonstrated that treatment with the proinflammatory cytokine TNF-α disrupted vascular endothelial cell-cell tight junctions and promoted monocyte endothelial cell adhesion. Western blotting and Sambucus nigra lectin (SNA) blotting analyses revealed that TNF-α treatment decreased α-2, 6-sialic acid transferase 1 (ST6Gal-I) levels and downregulated VE-Cadherin α-2, 6 sialylation...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28079060/intranasal-lactoferrin-enhances-%C3%AE-secretase-dependent-amyloid-precursor-protein-processing-via-the-erk1-2-creb-and-hif-1%C3%AE-pathways-in-an-alzheimer-s-disease-mouse-model
#9
Chuang Guo, Zhao-Hui Yang, Shuai Zhang, Rui Chai, Han Xue, Yan-Hui Zhang, Jia-Yi Li, Zhan-You Wang
Growing evidence suggests that lactoferrin (Lf), an iron-binding glycoprotein, is a pleiotropic functional nutrient. Additionally, Lf was recently implicated as a neuroprotective agent. These properties make Lf a valuable therapeutic candidate for the treatment of Alzheimer's disease (AD). However, the mechanisms regulating the physiological roles of Lf in the pathologic condition of AD remain unknown. In the present study, an APPswe/PS1DE9 transgenic mouse model of AD was used. We explored whether intranasal human Lf (hLf) administration could reduce β-amyloid (Aβ) deposition and ameliorate cognitive decline in this AD model...
January 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28078611/hyperbaric-oxygen-prevents-cognitive-impairments-in-mice-induced-by-d-galactose-by-improving-cholinergic-and-anti-apoptotic-functions
#10
Chunxia Chen, Luying Huang, Zhihuan Nong, Yaoxuan Li, Wan Chen, Jianping Huang, Xiaorong Pan, Guangwei Wu, Yingzhong Lin
Our previous study demonstrated that hyperbaric oxygen (HBO) improved cognitive impairments mainly by regulating oxidative stress, inflammatory responses and aging-related gene expression. However, a method for preventing cognitive dysfunction has yet to be developed. In the present study, we explored the protective effects of HBO on the cholinergic system and apoptosis in D-galactose (D-gal)-treated mice. A model of aging was established via systemic intraperitoneal injection of D-gal daily for 8 weeks. HBO was administered during the last 2 weeks of D-gal injection...
January 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28073379/tau-passive-immunization-inhibits-not-only-tau-but-also-a%C3%AE-pathology
#11
Chun-Ling Dai, Yunn Chyn Tung, Fei Liu, Cheng-Xin Gong, Khalid Iqbal
BACKGROUND: Accumulation of hyperphosphorylated tau protein is a histopathological hallmark of Alzheimer's disease (AD) and related tauopathies. Currently, there is no effective treatment available for these progressive neurodegenerative diseases. In recent years, tau immunotherapy has shown great potential in animal models. We report the effect of immunization with tau antibodies 43D against tau 6-18 and 77E9 against tau 184-195 on tau and amyloid-β (Aβ) pathologies and cognition in triple-transgenic (3×Tg)-AD mice at mild to moderate stages of the disease...
January 10, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28070499/metabolic-relationship-between-diabetes-and-alzheimer-s-disease-affected-by-cyclo-his-pro-plus-zinc-treatment
#12
REVIEW
Moon K Song, David S Bischoff, Albert M Song, Koichi Uyemura, Dean T Yamaguchi
BACKGROUND: Association of Alzheimer's Disease (AD) with Type 2 Diabetes (T2D) has been well established. Cyclo(His-Pro) plus zinc (Cyclo-Z) treatment ameliorated diabetes in rats and similar improvements have been seen in human patients. Treatment of amyloid precursor protein (APP) transgenic mice with Cyclo-Z exhibited memory improvements and significantly reduced Aβ-40 and Aβ-42 protein levels in the brain tissues of the mice. SCOPE OF REVIEW: Metabolic relationship between AD and T2D will be described with particular attention to insulin sensitivity and Aβ degradation in brain and plasma tissues...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28065363/relationship-between-amyloid-precursor-protein-in-seminal-plasma-and-abnormal-penile-sympathetic-skin-response-in-lifelong-premature-ejaculation
#13
Zhiwei Hong, Yuming Feng, Hualong Ding, Xuechun Hu, Jin-Chun Lu, Xie Ge, Yifeng Ge, Bing Yao
INTRODUCTION: Hyperactivity of the sympathetic nervous system can play an important role in lifelong premature ejaculation (PE). Our previous study found that amyloid precursor protein (APP) levels in seminal plasma of patients with PE were clearly increased. Amyloid-β (Aβ) is derived from APP. Excessive Aβ, especially Aβ42, can cause neuronal dysfunction. AIM: To determine whether APP and Aβ42 are associated with an abnormal penile sympathetic skin response (PSSR)...
January 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28065273/screening-and-characterization-strategies-for-nanobodies-targeting-membrane-proteins
#14
S Veugelen, M Dewilde, B De Strooper, L Chávez-Gutiérrez
The study of membrane protein function and structure requires their successful detection, expression, solubilization, and/or reconstitution, which poses a challenging task and relies on the availability of suitable tools. Several research groups have successfully applied Nanobodies in the purification, as well as the functional and structural characterization of membrane proteins. Nanobodies are small, single-chain antibody fragments originating from camelids presenting on average a longer CDR3 which enables them to bind in cavities and clefts (such as active and allosteric sites)...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28065262/analyzing-amyloid-%C3%AE-peptide-modulation-profiles-and-binding-sites-of-%C3%AE-secretase-modulators
#15
J Trambauer, A Fukumori, B Kretner, H Steiner
γ-Secretase is a key player in the pathogenesis of Alzheimer's disease (AD). The intramembrane-cleaving enzyme initially cleaves a C-terminal fragment of the amyloid precursor protein (APP) at the ɛ-site within its transmembrane domain to release the APP intracellular domain. Subsequent stepwise carboxy-terminal trimming cleavages eventually release amyloid-β (Aβ) peptides of 37-43 amino acids into the extracellular space. Aβ42 as well as the much less abundant Aβ43 species are highly aggregation prone and can deposit as plaques in the brains of affected patients, which are widely believed to be causative of AD...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28062666/cyclodextrin-has-conflicting-actions-on-autophagy-flux-in-vivo-in-brains-of-normal-and-alzheimer-model-mice
#16
Dun-Sheng Yang, Philip Stavrides, Asok Kumar, Ying Jiang, Panaiyur S Mohan, Masuo Ohno, Kostantin Dobrenis, Cristin D Davidson, Mitsuo Saito, Monika Pawlik, Chunfeng Huo, Steven U Walkley, Ralph A Nixon
2-hydroxypropyl-β-cyclodextrin (CYCLO), a modifier of cholesterol efflux from cellular membrane and endo-lysosomal compartments, reduces lysosomal lipid accumulations and has therapeutic effects in animal models of Niemann-Pick disease type C and several other neurodegenerative states. Here, we investigated CYCLO effects on autophagy in wild-type mice and TgCRND8 mice - an Alzheimer's Disease (AD) model exhibiting β-amyloidosis, neuronal autophagy deficits leading to protein and lipid accumulation within greatly enlarged autolysosomes...
January 5, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28059793/resveratrol-intervenes-in-the-cholesterol-and-isoprenoid-mediated-amyloidogenic-processing-of-a%C3%AE-pp-in-familial-alzheimer-s-disease
#17
Mohan Sathya, Ponnusamy Moorthi, Palanisamy Premkumar, Mahesh Kandasamy, Kesavan Swaminathan Jayachandran, Muthuswamy Anusuyadevi
Deterioration of cholesterol metabolism has recently been a frontier subject of investigation in the field of Alzheimer's disease (AD). Though amyloid-β protein precursor (AβPP) primes the pathological cascade, changes in cholesterol levels and its intermediates, geranyl geranyl pyrophosphate and farnesyl pyrophosphate, is expected to have a different consequence on AβPP processing and amyloid-β (Aβ) generation. However, the use of statins (HMG-COA reductase inhibitor) has been widely implicated in slowing down the pathogenic progression of AD, while the epidemiological reports on its biological effect remains controversial...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059792/quantitative-comparison-of-dense-core-amyloid-plaque-accumulation-in-amyloid-%C3%AE-protein-precursor-transgenic-mice
#18
Peng Liu, John H Reichl, Eshaan R Rao, Brittany M McNellis, Eric S Huang, Laura S Hemmy, Colleen L Forster, Michael A Kuskowski, David R Borchelt, Robert Vassar, Karen H Ashe, Kathleen R Zahs
There exist several dozen lines of transgenic mice that express human amyloid-β protein precursor (AβPP) with Alzheimer's disease (AD)-linked mutations. AβPP transgenic mouse lines differ in the types and amounts of Aβ that they generate and in their spatiotemporal patterns of expression of Aβ assemblies, providing a toolkit to study Aβ amyloidosis and the influence of Aβ aggregation on brain function. More complete quantitative descriptions of the types of Aβ assemblies present in transgenic mice and in humans during disease progression should add to our understanding of how Aβ toxicity in mice relates to the pathogenesis of AD...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28054918/app-modulates-kcc2-expression-and-function-in-hippocampal-gabaergic-inhibition
#19
Ming Chen, Jinzhao Wang, Jinxiang Jiang, Xingzhi Zheng, Nicholas J Justice, Kun Wang, Xiangqian Ran, Yi Li, Qingwei Huo, Jiajia Zhang, Hongmei Li, Nannan Lu, Ying Wang, Hui Zheng, Cheng Long, Li Yang
Amyloid precursor protein (APP) is enriched at the synapse, but its synaptic function is still poorly understood. We previously showed that GABAergic short-term plasticity is impaired in App knock-out (App(-/-)) animals, but the precise mechanism by which APP regulates GABAergic synaptic transmission has remained elusive. Using electrophysiological, biochemical, moleculobiological, and pharmacological analysis, here we show that APP can physically interact with KCC2, a neuron-specific K(+)-Cl(-) cotransporter that is essential for Cl(-) homeostasis and fast GABAergic inhibition...
January 5, 2017: ELife
https://www.readbyqxmd.com/read/28053144/excess-app-o-glycosylation-by-galnac-t6-decreases-a%C3%AE-production
#20
Keiko Akasaka-Manya, Masaki Kawamura, Hiroki Tsumoto, Yuko Saito, Yuriko Tachida, Shinobu Kitazume, Hiroyuki Hatsuta, Yuri Miura, Shin-Ichi Hisanaga, Shigeo Murayama, Yasuhiro Hashimoto, Hiroshi Manya, Tamao Endo
Alterations of the structure and/or amount of glycans present on proteins are associated with many diseases. We previously demonstrated that changes in N-glycans alter Aβ production. In the present study, we focused on the relationship between Alzheimer's disease (AD) and O-glycan, another type of glycan. The UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family functions in the first step of mucin-type O-glycan synthesis. Analysis of the expression of GalNAc-Ts in the human brain using real-time PCR revealed that the expression of several GalNAc-Ts was altered with sporadic AD progression...
January 2017: Journal of Biochemistry
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