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amyloid precursor protein

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https://www.readbyqxmd.com/read/28441965/evaluation-of-a-dna-a%C3%AE-42-vaccine-in-adult-rhesus-monkeys-macaca-mulatta-antibody-kinetics-and-immune-profile-after-intradermal-immunization-with-full-length-dna-a%C3%AE-42-trimer
#1
Doris Lambracht-Washington, Min Fu, Pat Frost, Roger N Rosenberg
BACKGROUND: Aggregated amyloid-β peptide 1-42 (Aβ42), derived from the cellular amyloid precursor protein, is one of the pathological hallmarks of Alzheimer's disease (AD). Although active immunization against Aβ42 peptide was successful in AD mouse models and led to removal of plaques and improved memory, a similar clinical trial in humans (Aβ42 peptide immunization with QS-21 adjuvant) was stopped in phase II, when 6% of the treated patients developed encephalitis. Currently ongoing passive immunizations with the injection of preformed monoclonal antibodies against different epitopes within the Aβ1-42 peptide, which do not lead to activation of the immune system, have shown some effects in slowing AD pathology...
April 26, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28441759/synaptic-homeostasis-and-its-immunological-disturbance-in-neuromuscular-junction-disorders
#2
REVIEW
Masaharu Takamori
In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor (nAChR) clustering, trans-synaptic communication and synaptic stabilization are modulated by the molecular mechanisms underlying synaptic plasticity. The synaptic functions are based presynaptically on the active zone architecture, synaptic vesicle proteins, Ca(2+) channels and synaptic vesicle recycling. Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized sensitivity to ACh, and synaptic stabilization via linkage to the extracellular matrix so as to be precisely opposed to the nerve terminal...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28439555/structural-and-biochemical-differences-between-the-notch-and-the-amyloid-precursor-protein-transmembrane-domains
#3
Catherine L Deatherage, Zhenwei Lu, Brett M Kroncke, Sirui Ma, Jarrod A Smith, Markus W Voehler, Robert L McFeeters, Charles R Sanders
γ-Secretase cleavage of the Notch receptor transmembrane domain is a critical signaling event for various cellular processes. Efforts to develop inhibitors of γ-secretase cleavage of the amyloid-β precursor C99 protein as potential Alzheimer's disease therapeutics have been confounded by toxicity resulting from the inhibition of normal cleavage of Notch. We present biochemical and structural data for the combined transmembrane and juxtamembrane Notch domains (Notch-TMD) that illuminate Notch signaling and that can be compared and contrasted with the corresponding traits of C99...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28434365/identification-of-amyloid-precursor-protein-from-autopsy-and-biopsy-specimens-using-lmd-lc-ms-ms-the-experience-at-kumamoto-university
#4
Masayoshi Tasaki, Mitsuharu Ueda, Konen Obayashi, Yumiko Kinoshita, Sayaka Matsumoto, Mayumi Mizukami, Teruaki Masuda, Yohei Misumi, Taro Yamashita, Yukio Ando
No abstract text is available yet for this article.
March 2017: Amyloid: the International Journal of Experimental and Clinical Investigation
https://www.readbyqxmd.com/read/28429536/%C3%AE-mangostin-decreases-%C3%AE-amyloid-peptides-production-via-modulation-of-amyloidogenic-pathway
#5
Lan-Xue Zhao, Yan Wang, Ting Liu, Yan-Xia Wang, Hong-Zhuan Chen, Jian-Rong Xu, Yu Qiu
AIMS: β-amyloid (Aβ) aggregation and deposition play a central role in the pathogenic process of Alzheimer's disease (AD). α-Mangostin (α-M), a polyphenolic xanthone, have been shown to dissociate Aβ oligomers. In this study, we further investigated the effect of α-M on Aβ production and its molecular mechanism. METHODS: The Aβ and soluble amyloid precursor protein α (sAPPα) in culture medium of cortical neurons were measured by ELISA. The activities of α-, β-, and γ-secretases were assayed, and the interaction between α-M and β- or γ-secretases was simulated by molecular docking...
April 21, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28428554/network-assisted-analysis-of-gwas-data-identifies-a-functionally-relevant-gene-module-for-childhood-onset-asthma
#6
Y Liu, M Brossard, C Sarnowski, A Vaysse, M Moffatt, P Margaritte-Jeannin, F Llinares-López, M H Dizier, M Lathrop, W Cookson, E Bouzigon, F Demenais
The number of genetic factors associated with asthma remains limited. To identify new genes with an undetected individual effect but collectively influencing asthma risk, we conducted a network-assisted analysis that integrates outcomes of genome-wide association studies (GWAS) and protein-protein interaction networks. We used two GWAS datasets, each consisting of the results of a meta-analysis of nine childhood-onset asthma GWASs (5,924 and 6,043 subjects, respectively). We developed a novel method to compute gene-level P-values (fastCGP), and proposed a parallel dense-module search and cross-selection strategy to identify an asthma-associated gene module...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424586/app-protein-family-signaling-at-the-synapse-insights-from-intracellular-app-binding-proteins
#7
REVIEW
Suzanne Guénette, Paul Strecker, Stefan Kins
Understanding the molecular mechanisms underlying amyloid precursor protein family (APP/APP-like proteins, APLP) function in the nervous system can be achieved by studying the APP/APLP interactome. In this review article, we focused on intracellular APP interacting proteins that bind the YENPTY internalization motif located in the last 15 amino acids of the C-terminal region. These proteins, which include X11/Munc-18-interacting proteins (Mints) and FE65/FE65Ls, represent APP cytosolic binding partners exhibiting different neuronal functions...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28423937/concordance-of-several-subcellular-interactions-initiates-alzheimer-s-dementia-their-reversal-requires-combination-treatment
#8
W J Fessel
The pathogenesis of Alzheimer's disease involves multiple pathways that, at the macrolevel, include decreased proliferation plus increased loss affecting neurons, astrocytes, and capillaries and, at the subcellular level, involve several elements: amyloid/amyloid precursor protein, presenilins, the unfolded protein response, the ubiquitin/proteasome system, the Wnt/catenin system, the Notch signaling system, mitochondria, mitophagy, calcium, and tau. Data presented show the intimate, anatomical interactions between neurons, astrocytes, and capillaries; the interactions between the several subcellular factors affecting those cells; and the treatments that are currently available and that might correct dysfunctions in the subcellular factors...
May 2017: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/28420695/adeno-associated-viral-9-mediated-cdk5-inhibitory-peptide-reverses-pathologic-changes-and-behavioral-deficits-in-the-alzheimer-s-disease-mouse-model
#9
Yong He, Suyue Pan, Miaojing Xu, Rongni He, Wei Huang, Pingping Song, Jianou Huang, Han-Ting Zhang, Yafang Hu
Cyclin-dependent kinase 5 (Cdk5), which binds to and is activated by p35, phosphorylates multiple substrates and plays an essential role in the development and function of the CNS; however, proteolytic production of p25 from p35 under stress conditions leads to the inappropriate activation of Cdk5 and contributes to hyperphosphorylation of τ and other substrates that are related to the pathogenesis of Alzheimer's disease. Selective inhibition of aberrant Cdk5 activity via genetic overexpression of Cdk5 inhibitory peptide (CIP) reduces pathologic changes and prevents brain atrophy and memory loss in p25-transgenic mice...
April 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28417423/evaluation-of-the-expression-of-amyloid-precursor-protein-and-the-ratio-of-secreted-amyloid-beta-42-to-amyloid-beta-40-in-sh-sy5y-cells-stably-transfected-with-wild-type-single-mutant-and-double-mutant-forms-of-the-app-gene-for-the-study-of-alzheimer-s-disease
#10
Aslina Pahrudin Arrozi, Siti Nur Syazwani Shukri, Wan Zurinah Wan Ngah, Yasmin Anum Mohd Yusof, Mohd Hanafi Ahmad Damanhuri, Suzana Makpol
Neuroblastoma cell lines such as SH-SY5Y are the most frequently utilized models in neurodegenerative research, and their use has advanced the understanding of the pathology of neurodegeneration over the past few decades. In Alzheimer's disease (AD), several pathogenic mutations have been described, all of which cause elevated levels of pathological hallmarks such as amyloid-beta (Aβ). Although the genetics of Alzheimer's disease is well known, familial AD only accounts for a small number of cases in the population, with the rest being sporadic AD, which contains no known mutations...
April 17, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28417146/repeated-mild-traumatic-brain-injury-in-female-rats-increases-lipid-peroxidation-in-neurons
#11
Nathanael J Yates, Stephen Lydiard, Brooke Fehily, Gillian Weir, Aaron Chin, Carole A Bartlett, Jacqueline Alderson, Melinda Fitzgerald
Negative outcomes of mild traumatic brain injury (mTBI) can be exacerbated by repeated insult. Animal models of repeated closed-head mTBI provide the opportunity to define acute pathological mechanisms as the number of mTBI increases. Furthermore, little is known about the effects of mTBI impact site, and how this may affect brain function. We use a closed head, weight drop model of mTBI that allows head movement following impact, in adult female rats to determine the role of the number and location of mTBI on brain pathology and behaviour...
April 17, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28416393/tdp-43-expression-influences-amyloid%C3%AE-plaque-deposition-and-tau-aggregation
#12
Stephani A Davis, Kok Ann Gan, James A Dowell, Nigel J Cairns, Michael A Gitcho
Although the main focus in Alzheimer's disease (AD) has been an investigation of mechanisms causing Aβ plaque deposition and tau tangle formation, recent studies have shown that phosphorylated TDP-43 pathology is present in up to 50% of sporadic cases. Furthermore, elevated phosphorylated TDP-43 has been associated with more severe AD pathology. Therefore, we hypothesized that TDP-43 may regulate amyloid-beta precursor protein (APP) trafficking and tau phosphorylation/aggregation. In order to examine the role of TDP-43 in AD, we developed a transgenic mouse that overexpresses hippocampal and cortical neuronal TDP-43 in a mouse expressing familial mutations (K595N and M596L) in APP and presenilin 1 (PSEN1ΔE9)...
April 20, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28414207/defining-the-minimum-substrate-and-charge-recognition-model-of-gamma-secretase
#13
Yan Yan, Ting-Hai Xu, Karsten Melcher, H Eric Xu
γ-Secretase is an intramembrane aspartyl protease that cleaves the C99 fragment of amyloid precursor protein to generate extracellular Aβ peptides. These peptides can oligomerize and aggregate to form amyloid plaques, processes that are widely believed to be causal for Alzheimer's disease. In spite of this critical function, it remains unknown how γ-secretase recognizes C99 and its other substrates, including Notch. In this study we determined E22-K55 as the minimal C99 fragment that was sufficient and required for initial cleavage...
April 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28413985/salvianolic-acid-b-decreases-the-generation-of-amyloid-%C3%AE-by-modulating-bace1-activity
#14
Siva Sundara Kumar Durairajan, Venkat Reddy Chirasani, Sravan Gopalakrishnan Shetty, Ashok Iyaswamy, Sandeep Malampati, Juxian Song, Liangfeng Liu, Jiandong Huang, Sanjib Senapati, Min Li
Generation and accumulation of the amyloid-β (Aβ) peptide after proteolytic processing of the full length amyloid precursor protein (FL-APP) by β-secretase (β-site APP cleaving enzyme or BACE1) and β -secretase is a main causal factor of Alzheimer's disease (AD). Thus, inhibition of BACE1, a rate-limiting enzyme in the production of Aβ, is an attractive therapeutic approach for the treatment of AD. Recent studies suggest that salvianolic acid B (Sal B) isolated from the radix of Salvia miltiorrhiza Bunge, a Chinese herbal medicine commonly used for the treatment of cardiovascular, cerebrovascular and liver diseases in China...
April 17, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28413924/erythropoietin-attenuates-axonal-injury-after-middle-cerebral-artery-occlusion-in-mice
#15
Rongliang Wang, Haiping Zhao, Jincheng Li, Yunxia Duan, Zhibin Fan, Zhen Tao, Fei Ju, Feng Yan, Yumin Luo
OBJECTIVE: Erythropoietin (EPO) confers potent neuroprotection against ischemic injury through a variety of mechanisms. However, the protective effect of EPO on axons after cerebral ischemia in adult mice is rarely covered. The purpose of this study was to investigate the potential neuroprotective effects of EPO on axons in mice after cerebral ischemia. METHODS: A total of 30 adult male C57 BL/6 mice were treated with EPO (5000 IU/kg) or vehicle after transient middle cerebral artery occlusion (MCAO)...
April 16, 2017: Neurological Research
https://www.readbyqxmd.com/read/28413833/beneficial-effects-of-a-pyrroloquinolinequinone-containing-dietary-formulation-on-motor-deficiency-cognitive-decline-and-mitochondrial-dysfunction-in-a-mouse-model-of-alzheimer-s-disease
#16
Darrell Sawmiller, Song Li, Takashi Mori, Ahsan Habib, David Rongo, Vedad Delic, Patrick C Bradshaw, R Douglas Shytle, Cyndy Sanberg, Paula Bickford, Jun Tan
Alzheimer's disease (AD), a progressive neurodegenerative disorder, is linked to oxidative stress, altered amyloid precursor protein (APP) proteolysis, tau hyperphosphorylation and the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFT). A growing body of evidence suggests that mitochondrial dysfunction can be a key promoter of all of these pathologies and predicts that restoration of mitochondrial function might be a potential therapeutic strategy for AD. Therefore, in the present study, we tested the beneficial effect of a nutraceutical formulation Nutrastem II (Nutra II), containing NT020 (a mitochondrial restorative and antioxidant proprietary formulation) and pyrroloquinolinequinone (PQQ, a stimulator of mitochondria biogenesis) in 5XFAD transgenic mice...
April 2017: Heliyon
https://www.readbyqxmd.com/read/28413720/direct-imaging-of-app-proteolysis-in-living-cells
#17
Niccoló Parenti, Ambra Del Grosso, Claudia Antoni, Marco Cecchini, Renato Corradetti, Francesco S Pavone, Martino Calamai
Alzheimer's disease is a multifactorial disorder caused by the interaction of genetic, epigenetic and environmental factors. The formation of cytotoxic oligomers consisting of Aβ peptide is widely accepted as being one of the main key events triggering the development of Alzheimer's disease. Aβ peptide production results from the specific proteolytic processing of the amyloid precursor protein (APP). Deciphering the factors governing the activity of the secretases responsible for the cleavage of APP is still a critical issue...
2017: PeerJ
https://www.readbyqxmd.com/read/28413462/identification-of-mirna-biomarkers-of-pneumonia-using-rna-sequencing-and-bioinformatics-analysis
#18
Sai Huang, Cong Feng, Yong-Zhi Zhai, Xuan Zhou, Bei Li, Li-Li Wang, Wei Chen, Fa-Qin Lv, Tan-Shi Li
Pneumonia is a lower respiratory tract infection that causes dramatic mortality worldwide. The present study aimed to investigate the pathogenesis of pneumonia and identify microRNA (miRNA) biomarkers as candidates for targeted therapy. RNA from the peripheral blood plasma of participants with pneumonia (severe, n=9; non-severe, n=9) and controls (n=9) was isolated and paired-end sequencing was performed on an Illumina HiSeq4000 system. Following the processing of raw reads, the sequences were aligned against the Genome Reference Consortium human genome assembly 38 reference genome using Bowtie2 software...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28411010/effects-of-vitamin-d-and-resveratrol-on-metabolic-associated-markers-in-liver-and-adipose-tissue-from-samp8-mice
#19
Yehua Rui, Jinbo Cheng, Liqiang Qin, Cheng Shan, Jie Chang, Guiping Wang, Zhongxiao Wan
SAMP8 mice exhibit multiple metabolic characteristics associated with age, and it is a suitable candidate for researching aging associated metabolic dysfunction. OBJECTIVES: We aimed to 1) explore how key metabolic markers will be altered in both liver and adipose tissue with aging in SAMP8 mice; and 2) how the combination of vitamin D (VD) with resveratrol (RSV) will affect aging associated metabolic impairment in liver and adipose tissue from SAMP8 mice. METHODS: SAMP8 mice and their control SAMR1 mice were divided into 5 groups, i...
April 11, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28410378/metabolic-changes-and-inflammation-in-cultured-astrocytes-from-the-5xfad-mouse-model-of-alzheimer-s-disease-alleviation-by-pantethine
#20
Manuel van Gijsel-Bonnello, Kévin Baranger, Philippe Benech, Santiago Rivera, Michel Khrestchatisky, Max de Reggi, Bouchra Gharib
Astrocytes play critical roles in central nervous system homeostasis and support of neuronal function. A better knowledge of their response may both help understand the pathophysiology of Alzheimer's disease (AD) and implement new therapeutic strategies. We used the 5xFAD transgenic mouse model of AD (Tg thereafter) to generate astrocyte cultures and investigate the impact of the genotype on metabolic changes and astrocytes activation. Metabolomic analysis showed that Tg astrocytes exhibited changes in the glycolytic pathway and tricarboxylic acid (TCA) cycle, compared to wild type (WT) cells...
2017: PloS One
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