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https://www.readbyqxmd.com/read/28733814/neuroprotective-effect-of-ipriflavone-against-scopolamine-induced-memory-impairment-in-rats
#1
Hani S Hafez, Doaa A Ghareeb, Samar R Saleh, Mariam M Abady, Maha A El Demellawy, Hend Hussien, Nihad Abdel-Monem
BACKGROUND: Alzheimer's disease is an age-related neurodegenerative disorder characterized clinically by a progressive loss of memory and cognitive functions resulting in severe dementia. Ipriflavone (IPRI) is a non-hormonal, semi-synthetic isoflavone, clinically used in some countries for the treatment and prevention of postmenopausal osteoporosis. Moreover, ipriflavone is a non-peptidomimetic small molecule AChE inhibitor with an improved bioavailability after systemic administration, due to its efficient blood-brain barrier permeability in comparison with peptidomimetic inhibitors...
July 22, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28729535/pld1-promotes-dendritic-spine-development-by-inhibiting-adam10-mediated-n-cadherin-cleavage
#2
Li-Da Luo, Gang Li, Yun Wang
Synapses are the basic units of information transmission, processing and integration in the nervous system. Dysfunction of the synaptic development has been recognized as one of the main reasons for mental dementia and psychiatric diseases such as Alzheimer's disease and autism. However, the underlying mechanisms of the synapse formation are far from clear. Here we report that phospholipase D1 (PLD1) promotes the development of dendritic spines in hippocampal neurons. We found that overexpressing PLD1 increases both the density and the area of dendritic spines...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28722189/adam10-modulates-calcitriol-regulated-rage-in-cardiomyocytes
#3
Ting-Wei Lee, Yu-Hsun Kao, Ting-I Lee, Yi-Jen Chen
BACKGROUND: Receptor for advanced glycation end products (RAGE) signaling plays a critical role in the pathogenesis of cardiovascular disease. Calcitriol modulates cardiac RAGE expression. This study explored the mechanisms underlying the effect of calcitriol on RAGE and soluble RAGE (sRAGE) expression in cardiomyocytes. METHODS: Western blot, ELISA, fluorometric assay and PCR analyses were used to evaluate the RAGE, sRAGE, endogenous secretory RAGE (esRAGE), Jun N-terminal kinase (JNK), and a disintegrin and metalloprotease 10 (ADAM10) expression and enzyme activity in HL-1 atrial myocytes without and with calcitriol (10 and 100 nM), nuclear factor-κB (NF-κB) inhibitor (50 μg/mL), or ADAM10 inhibitor (5 μM) incubation for 48 hours...
July 19, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28707894/vitamin-d-receptor-regulates-amyloid-beta-1-42-production-with-protein-disulfide-isomerase-a3
#4
Duygu Gezen-Ak, Irem L Atasoy, Esin Candas, Merve Alaylioglu, Selma Yilmazer, Erdinc Dursun
The challenge of understanding the biology of neuronal amyloid processing could provide a basis for understanding the amyloid pathology in Alzheimer's disease (AD). Based on our previous studies we have suggested that AD might be the consequence of a hormonal imbalance in which the critical hormone is vitamin D. The present study primarily focused on the creation of a condition that prevents the genomic or non-genomic action of vitamin D by disrupting vitamin D receptors (VDR or PDIA3/1,25MARRS); the effects of these disruptions on the series of proteins involved in secretases that play a crucial role in amyloid pathology and on amyloid beta (Aβ) production in primary cortical neurons were observed...
July 14, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28703811/cytoplasmic-fragment-of-cd147-generated-by-regulated-intramembrane-proteolysis-contributes-to-hcc-by-promoting-autophagy
#5
Bo Wu, Jian Cui, Xiang-Min Yang, Zhen-Yu Liu, Fei Song, Ling Li, Jian-Li Jiang, Zhi-Nan Chen
Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers worldwide. CD147 (EMMPRIN or basigin) is a leading gene relating to hepatocarcinogenesis and metastasis, and is detected in transmembrane, exosome or circulating forms in HCC patients. The endosome recycling of CD147 further enhances the function of this oncoprotein from a dynamic perspective. However, previous studies about CD147 mainly focused on one separate form, and little attention has been paid to how the different forms of tumor-derived CD147 changes...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28703301/the-xenoestrogens-biphenol-a-and-nonylphenol-differentially-regulate-metalloprotease-mediated-shedding-of-egfr-ligands
#6
Paulina Urriola-Muñoz, Xue Li, Thorsten Maretzky, David R McIlwain, Tak W Mak, Juan G Reyes, Carl P Blobel, Ricardo D Moreno
The xenoestrogens Bisphenol-A (BPA) and Nonylphenol (NP) are endocrine disruptors used in the plastic polymer industry to manufacture different products for human use. Previous studies have suggested a role of these compounds in the shedding of signaling molecules, such as tumor necrosis factor α (TNF- α). The aim of this work was to evaluate the effect of BPA and NP on the sheddase ADAM17 and its newly discovered regulators iRhom1 and iRhom2 in the release of EGFR-ligands. We report that BPA and NP can stimulate the release of the ADAM17-substrates HB-EGF and TGF- α...
July 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28698968/inhibition-of-poly-adp-ribose-polymerase-1-enhances-gene-expression-of-selected-sirtuins-and-app-cleaving-enzymes-in-amyloid-beta-cytotoxicity
#7
Przemysław L Wencel, Walter J Lukiw, Joanna B Strosznajder, Robert Piotr Strosznajder
Poly(ADP-ribose) polymerases (PARPs) and sirtuins (SIRTs) are involved in the regulation of cell metabolism, transcription, and DNA repair. Alterations of these enzymes may play a crucial role in Alzheimer's disease (AD). Our previous results indicated that amyloid beta (Aβ) peptides and inflammation led to activation of PARP1 and cell death. This study focused on a role of PARP1 in the regulation of gene expression for SIRTs and beta-amyloid precursor protein (βAPP) cleaving enzymes under Aβ42 oligomers (AβO) toxicity in pheochromocytoma cells (PC12) in culture...
July 12, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28687716/regulation-of-the-trafficking-and-the-function-of-the-metalloprotease-adam10-by-tetraspanins
#8
REVIEW
Julien Saint-Pol, Etienne Eschenbrenner, Emmanuel Dornier, Claude Boucheix, Stéphanie Charrin, Eric Rubinstein
By interacting directly with partner proteins and with one another, tetraspanins organize a network of interactions referred to as the tetraspanin web. ADAM10 (A Disintegrin And Metalloprotease 10), an essential membrane-anchored metalloprotease that cleaves off the ectodomain of a large variety of cell surface proteins including cytokines, adhesion molecules, the precursor of the β-amyloid peptide APP or Notch, has emerged as a major component of the tetraspanin web. Recent studies have shown that ADAM10 associates directly with all members (Tspan5, Tspan10, Tspan14, Tspan15, Tspan17 and Tspan33) of a subgroup of tetraspanins having eight cysteines in the large extracellular domain and referred to as TspanC8...
July 7, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28669545/retrograde-synaptic-inhibition-is-mediated-by-%C3%AE-neurexin-binding-to-the-%C3%AE-2%C3%AE-subunits-of-n-type-calcium-channels
#9
Xia-Jing Tong, Eduardo Javier López-Soto, Lei Li, Haowen Liu, Daniel Nedelcu, Diane Lipscombe, Zhitao Hu, Joshua M Kaplan
The synaptic adhesion molecules Neurexin and Neuroligin alter the development and function of synapses and are linked to autism in humans. In C. elegans, post-synaptic Neurexin (NRX-1) and pre-synaptic Neuroligin (NLG-1) mediate a retrograde synaptic signal that inhibits acetylcholine (ACh) release at neuromuscular junctions. Here, we show that the retrograde signal decreases ACh release by inhibiting the function of pre-synaptic UNC-2/CaV2 calcium channels. Post-synaptic NRX-1 binds to an auxiliary subunit of pre-synaptic UNC-2/CaV2 channels (UNC-36/α2δ), decreasing UNC-36 abundance at pre-synaptic elements...
July 19, 2017: Neuron
https://www.readbyqxmd.com/read/28656294/overexpression-of-a-disintegrin-and-metalloprotease-10-promotes-tumor-proliferation-migration-and-poor-prognosis-in-hypopharyngeal-squamous-cell-carcinoma
#10
Chuanjin Ding, Qicheng Zhang, Yan Chen, Xiaobo Zhang, Pei Wu, Zhenxin Zhang
The aim of this study was to determine the effect of A disintegrin and metalloprotease 10 (ADAM10) protein expression on the progression, migration and prognosis of hypopharyngeal squamous cell carcinoma (HSCC). Immunohistochemistry and western blot analysis were performed to detect ADAM10 expression in human HSCC specimens. Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis and wound-healing assay were employed to investigate the effects of ADAM10 knockdown (ADAM10-RNAi) on major oncogenic properties of FaDu cells...
June 27, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28625569/synaptic-dysfunction-in-alzheimer-s-disease-from-the-role-of-amyloid-%C3%AE-peptide-to-the-%C3%AE-secretase-adam10
#11
Stefano Musardo, Elena Marcello
Alzheimer's disease (AD) is emerging as the most prevalent and socially disruptive illness of aging populations as more people live long enough to become affected. Although AD is placing a considerable and increasing burden on patients, caregivers and society, it represents the largest unmet medical need in neurology, because it is currently incurable. In the last few years, the amyloid hypothesis, which points to amyloid β-peptide (Aβ) as the initiating factor in AD, had a central role in the development of therapeutic strategies for AD...
June 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28624438/the-metalloproteinase-adam10-a-useful-therapeutic-target
#12
REVIEW
Sebastian Wetzel, Lisa Seipold, Paul Saftig
Proteolytic cleavage represents a unique and irreversible posttranslational event regulating the function and half-life of many intracellular and extracellular proteins. The metalloproteinase ADAM10 has raised attention since it cleaves an increasing number of protein substrates close to the extracellular membrane leaflet. This "ectodomain shedding" regulates the turnover of a number of transmembrane proteins involved in cell adhesion and receptor signaling. It can initiate intramembrane proteolysis followed by nuclear transport and signaling of the cytoplasmic domain...
June 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28624437/the-plasma-membrane-penultimate-regulator-of-adam-sheddase-function
#13
REVIEW
Karina Reiss, Sucharit Bhakdi
BACKGROUND: ADAM10 and ADAM17 are the best characterized members of the ADAM (A Disintegrin and Metalloproteinase) - family of transmembrane proteases. Both are involved diverse physiological and pathophysiological processes. ADAMs are known to be regulated by posttranslational mechanisms. However, emerging evidence indicates that the plasma membrane with its unique dynamic properties may additionally play an important role in controlling sheddase function. SCOPE OF REVIEW: Membrane events that could contribute to regulation of ADAM-function are summarized...
June 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28624220/tat-hafgf14-154-upregulates-adam10-to-attenuate-the-alzheimer-phenotype-of-app-ps1-mice-through-the-pi3k-creb-ire1%C3%AE-xbp1-pathway
#14
Tian Meng, Qin Cao, Peng Lei, Ashley I Bush, Qi Xiang, Zhijian Su, Xiang He, Jack T Rogers, Ing-Ming Chiu, Qihao Zhang, Yadong Huang
Acid fibroblast growth factor (aFGF) has shown neuroprotection in Alzheimer's disease (AD) models in previous studies, yet its mechanism is still uncertain. Here we report that the efficacy of Tat-haFGF14-154 is markedly increased when loaded cationic liposomes for intranasal delivery are intranasally administered to APP/PS1 mice. Our results demonstrated that liposomal Tat-haFGF14-154 treatment significantly ameliorated behavioral deficits, relieved brain Aβ burden, and increased the expression and activity of disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in the brain...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28620033/scissor-sisters-regulation-of-adam10-by-the-tspanc8-tetraspanins
#15
REVIEW
Alexandra L Matthews, Justyna Szyroka, Richard Collier, Peter J Noy, Michael G Tomlinson
A disintegrin and metalloprotease 10 (ADAM10) is a ubiquitously expressed transmembrane protein which is essential for embryonic development through activation of Notch proteins. ADAM10 regulates over 40 other transmembrane proteins and acts as a 'molecular scissor' by removing their extracellular regions. ADAM10 is also a receptor for α-toxin, a major virulence factor of Staphylococcus aureus Owing to the importance of its substrates, ADAM10 is a potential therapeutic target for cancer, neurodegenerative diseases such as Alzheimer's and prion diseases, bacterial infection and inflammatory diseases such as heart attack, stroke and asthma...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28614064/ionising-radiation-increases-permeability-of-endothelium-through-adam10-mediated-cleavage-of-ve-cadherin
#16
Sylwia Kabacik, Ken Raj
The association between ionising radiation (IR) exposure and risk of cardiovascular diseases (CVD) is well documented, but the underlying mechanism is still poorly understood. As atherosclerotic plaques are the most common cause of CVD, we investigated the effects of IR on one of the critical parameters for atherosclerotic plaque formation - endothelium permeability to macromolecules.We used endothelial cells from human coronary artery as a model of the endothelial layer. Our results show that exposure of this endothelial layer to IR increased its permeability to macromolecules of various sizes in a dose-dependent manner...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611181/ligand-activated-notch-undergoes-dtx4-mediated-ubiquitylation-and-bilateral-endocytosis-before-adam10-processing
#17
Patricia Chastagner, Eric Rubinstein, Christel Brou
The Notch signaling pathway, which is activated by cell-cell contact, is a major regulator of cell fate decisions. Mammalian Notch1 is present at the cell surface as a heterodimer of the Notch extracellular domain associated with the transmembrane and intracellular domains. After ligand binding, Notch undergoes proteolysis, releasing the Notch intracellular domain (NICD) that regulates gene expression. We monitored the early steps of activation with biochemical analysis, immunofluorescence analysis, and live-cell imaging of Notch1-expressing cells...
June 13, 2017: Science Signaling
https://www.readbyqxmd.com/read/28603494/yxqn-reduces-alzheimer-s-disease-like-pathology-and-cognitive-decline-in-appsweps1de9-transgenic-mice
#18
Xiaowan Wang, Runmin Song, Wenliang Lu, Ziyu Liu, Lichun Wang, Xiaojuan Zhu, Yanjun Liu, Zijie Sun, Jiang Li, Xiaomeng Li
Alzheimer's disease (AD) is the world's most common form of dementia, in which aggregation of amyloid-β (Aβ) is the hallmark. Unfortunately, few medicines have succeeded to completely cure AD. Yangxue Qingnao (YXQN) is a Chinese traditional medicine, and its pharmacological effect is improving cerebral blood flow. In this study, we firstly demonstrated that YXQN reduced AD-like pathology and cognitive impairment in APPswePS1dE9 (APP/PS1) mice with 2 months administration. Our data showed that YXQN substantially ameliorated behavioral defects in 10-month old APP/PS1 mice using Morris Water Maze and Y-maze tests, in which the cognitive ability of YXQN high-dose group approaches to wild type mice...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28600292/adam10-interacting-tetraspanins-tspan5-and-tspan17-regulate-ve-cadherin-expression-and-promote-t-lymphocyte-transmigration
#19
Jasmeet S Reyat, Myriam Chimen, Peter J Noy, Justyna Szyroka, G Ed Rainger, Michael G Tomlinson
The recruitment of blood leukocytes across the endothelium to sites of tissue infection is central to inflammation, but also promotes chronic inflammatory diseases. A disintegrin and metalloproteinase 10 (ADAM10) is a ubiquitous transmembrane molecular scissor that is implicated in leukocyte transmigration by proteolytically cleaving its endothelial substrates. These include VE-cadherin, a homotypic adhesion molecule that regulates endothelial barrier function, and transmembrane chemokines CX3CL1 and CXCL16, which have receptors on leukocytes...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28533442/the-role-of-shed-prp-c-in-the-neuropathogenesis-of-hiv-infection
#20
Bezawit W Megra, Eliseo A Eugenin, Joan W Berman
HIV-1 enters the CNS soon after peripheral infection and causes chronic neuroinflammation and neuronal damage that leads to cognitive impairment in 40-70% of HIV-infected people. The nonpathogenic cellular isoform of the human prion protein (PrP(c)) is an adhesion molecule constitutively expressed in the CNS. Previously, our laboratory showed that shed PrP(c) (sPrP(c)) is increased in the cerebrospinal fluid of HIV-infected people with cognitive deficits as compared with infected people with no impairment. In this article, we demonstrate that CCL2 and TNF-α, inflammatory mediators that are elevated in the CNS of HIV-infected people, increase shedding of PrP(c) from human astrocytes by increasing the active form of the metalloprotease ADAM10...
May 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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