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Tài liệu Molecular Neurobiology of Alzheimer Disease and Related Disorders doc
... each drug for any change in indications and dosage and for added warnings and precautions This is particularly important when the recommended agent is a new and/ or infrequently employed drug All ... clinical, basic and social sciences It is essential to promote the understanding of this formidable disease and to share new findings among researchers in the field Clinical and basic research ... induction of pro-inflammatory cytokines CD11b, iNOS and COX-2 mRNA Synapse and neuron dysfunction and loss Curcumin suppresses A-induced loss of NR2B and PSD-95, synaptic markers essential for memory...
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Báo cáo khoa học: "Upregulated but insufficient generation of activated protein C is associated with development of multiorgan failure in severe acute pancreatitis" pot
... and LK executed the study and drafted the manuscript LK, JAF, JHG, PP, HR, and JP participated in the original design and coordination of the study, and in writing the original protocol JAF and ... between HLA-DR expression and the PC and APC levels may therefore support the concept of interaction between inflammation and the PC pathway In severe AP, levels of PC and APC were moderately associated ... JHG carried out the PC and APC assays LK, PM, HR, and JP analysed the data PM, EK, PP, HR, and JP assisted in drafting the manuscript RH assisted in the original design and drafting of the final...
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Báo cáo khoa học: In vitro gamma-secretase cleavage of the Alzheimer’s amyloid precursor protein correlates to a subset of presenilin complexes and is inhibited by zinc potx
... similar to Ab and an e-CTF when transformed with MC99-3FLAG (A) Schematic of proteins (B) Lysate from MC99-3FLAGexpressing E coli, c and e standards were separated by SDS ⁄ PAGE and western blotted ... slightly faster mobility than the c-3FLAG standard (Fig 3C, lane 1) Using C101-3FLAG, c-3FLAG and e-3FLAG standards as molecular mass markers, the FLAG-reactive band migrating below C101-3FLAG is calculated ... PS2 and mature and immature Nct could be found in low molecular mass fractions Thus 0.5% CHAPSO during chromatography abolishes c-secretase activity and causes a subset of both Nct isoforms and...
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The effect of s1p lyase deficiency on the metabolism of the alzheimer’s related amyloid precursor protein
... trafficking and localization of APP and GSLs Cer is generated in the ER and further metabolized to GSLs in the Golgi compartments Both GSLs and APP are transported in secretory vesicles to the PM and ... confluency and briefly washed x with PBS and x with DMEM -/- Volume of transfection medium (DMEM-/-), amount of DNA and appropriate volume of transfection reagent were chosen and handled according ... of S1Plyase impairs the β- and γ-secretase dependent processing of APP on one hand, but also decreased the lysosomal degradation of APP and its CTFs on the other hand The increase of lysosomal...
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Tài liệu Báo cáo khoa học: Animal models of amyloid-b-related pathologies in Alzheimer’s disease docx
... leading to hemorrhage and perivascular microgliosis and astrocytosis The Dutch and Iowa mutations both reduce the negative charge of Ab and stimulate the formation of amyloid fibrils and attachment to ... cerebrospinal fluid (CSF) and plasma of young transgenic mice and healthy human Measures in PDAPP refer to Ab 1–x, in Tg2576, APP23 and humans to the sum of Ab1–40 and Ab1–42, and in tgArcSwe they ... that metal ions like Zn2+ and Cu2+ play a role in Ab biology, and possibly in AD pathogenesis Both ions bind APP and Ab with high affinity, and stimulate Ab aggregation and oxidizing effects of...
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Tài liệu Báo cáo khoa học: A facile method for expression and purification of the Alzheimer’s disease-associated amyloid b-peptide pdf
... supplied with the enzyme, and contained Aba, Abb and Abc at 40 nm each, and the start and stop primers Abstart and Abstop at 600 nm each, and 200 lm each of dATP, dCTP, dGTP and dTTP The product was ... Ab(1–40) and Ab(M1–40) are at least 97% pure In the lanes containing Ab(1–42) and Ab(M1– 42), there were prominent bands at approximately kDa and faint bands at approximately 14 kDa The band at ... by side with Ab(1–40) and Ab(1–42) synthesized using standard Fmoc chemistry and isolated by SEC as described above Thioflavin T binds to Ab fibrils and protofibrils [30], and has been extensively...
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Báo cáo khoa học: Selecting cells with different Alzheimer’s disease c-secretase activity using FACS Differential effect of presenilin exon 9 deletion on c- and e-cleavage doc
... substrate-activator and reporter genes yielded fluorescent cells Double-transfected COS-7 cells were fixed and observed by phase (panels and 3) and fluorescence microscopy (panels and 4) Phase microscopy ... Reinhard and A Weidemann for providing DNA-constructs and advice, and Ms F Katsis for protein sequencing We thank Dr M Shearman and Dr M Bogyo for providing inhibitors We thank Drs S Mok, A Hill and ... (5Gal-E1b-EGFP) DNA constructs into COS-7 and CHO cells resulted in the expression of GFP positive cells Figure 1B shows phase (panels and 3) and fluorescence microscopy (panels and 4) of COS-7 cells transfected...
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Báo cáo khoa học: Amyloid-b protofibril levels correlate with spatial learning in Arctic Alzheimer’s disease transgenic mice docx
... committees and performed in compliance with national and local animal care and use guidelines (protocols #C258 ⁄ and #C242 ⁄ at Uppsala University and #M2804 and #M2814 at the University of South Florida) ... impaired, but aged PSAPP mice exhibit robust and progressive deficits in learning and memory tests [31,32], and some data imply a correlation of deposited Ab and memory dysfunction [33], whereas other ... al In spite of similarities and obvious differences between animal models and human disease, it is still interesting and important to reflect upon these observations and to try to provide explanations...
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Báo cáo khoa học: Amyloid–cholinesterase interactions Implications for Alzheimer’s disease pot
... more and larger plaques than control animals, and some behavioral deterioration, as shown by the working memory test [17] By contrast, when two acetylcholinesterase inhibitors: physostigmine and ... presented Km and Vmax values higher than those observed by the free enzyme and was more resistant to: (b) incubation under low pH conditions, (c) inhibition by anti-cholinesterase agents and (d) inhibition ... and scrapie: mechanistic truths and physiological consequences of the timedependent solubility of amyloid proteins Annu Rev Biochem 66, 385–407 Inestrosa NC & Perelman A (1989) Distribution and...
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Báo cáo khoa học: High-resolution NMR studies of the zinc-binding site of the Alzheimer’s amyloid b-peptide pdf
... conditions, zinc binding occurs with His6, His13, His14 and Asp1 as ligands The binding seems to be specific and affects mainly the ligands and the neighboring residues The detected residue-specific ... 10 mM phosphate buffer at pH 7.4 and 286 K without (black) and with (red) 30 lM zinc as chloride (red) The d and e resonances of the histidines shown in (A) and (B), respectively, show significant ... 10 and 50 mm Hepes buffer at pH 7.2 and with 0, 10 and 20 lm Zn2+ Under these conditions, the dissociation constant for the Ab(1–28)–copper interaction was determined to be 2.5 ± 0.2 lm, and...
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Báo cáo khoa học: Shedding of the amyloid precursor protein-like protein APLP2 by disintegrin-metalloproteinases Retinoic acid-induced upregulation of substrate and proteinase ADAM10 during neuronal cell differentiation ppt
... matrixmetalloproteinases (MMPs) and ADAMs, decreased basal APPsa and APLP2s secretion to 60 and 75%, respectively, of untreated cells (Fig 2A,B, lanes and 3) and reduced the PMA-stimulated amount ... apparent molecular mass between 130 and 170 kDa (Fig 1) Two minor sharp bands between 95 and 120 kDa probably represent, according to earlier studies, APLP2s and truncated APLP2s without CS-GAG-modification ... mammalian APP-related protein APLP2 by the disintegrin and metalloproteinases ADAM10 and TACE (ADAM17), and a common upregulation of ADAM10 and its substrate by RA The main criteria for the involvement...
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báo cáo hóa học: " Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer''''s disease" potx
... patient brain and show an increased production of inflammatory markers such as COX-2, PGE2 and also increased levels of the pro-inflammatory cytokines IFN-γ and IL-12, TNF-α, IL-1α, IL-1β and IL-6 ... 15 fold more Aβ1–40, and 20 fold more 1– 42) but there was considerable slice-to-slice variation in soluble and insoluble Aβ levels within and between genotypes The TgAPPsw and PS1/APPsw mice express ... 31:657-60 Tarkowski E, Wallin A, Regland B, Blennow K, Tarkowski A: Local and systemic GM-CSF increase in Alzheimer's disease and vascular dementia Acta Neurol Scand 2001, 103:166-74 Lim GP, Yang...
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báo cáo hóa học: " Toll-like receptor 2 -196 to -174 del polymorphism influences the susceptibility of Han Chinese people to Alzheimer’s disease" potx
... contributions LT and JTY contributed to the design of the study JTY, SMM, LZW, CXM and LT were involved in sample acquisition and processing JTY, SMM, and LZW performed the statistical analyses JTY and LT ... according to the criteria of National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s disease and Related Disorders Association (NINCDS-ADRDA) [14] All AD cases ... calculating the D’ and r2 statistics These were found to be in weak linkage disequilibrium (D’ = 0.376 and r = 0.009) Hence, haplotype frequencies were not estimated, and both the GT repeat and the -196...
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Báo cáo y học: " Research In silico modeling of the specific inhibitory potential of thiophene-2,3-dihydro-1,5-benzothiazepine against BChE in the formation of β-amyloid plaques associated with Alzheimer''''s disease" doc
... (each), Max T = 23.03 for Trp84 and 32.22 for Trp279, and Mean T = 16.962 for Trp84 and 19.214 for Trp279) Maximum 2000 minimization cycles (for flexible residues and ligand) along with the maximum ... search algorithms and scoring functions Ligand docking studies were performed by MVD, which has recently been introduced and gained attention among medicinal chemists MVD is a fast and flexible docking ... repositioning of the selected side chains and minimization of ligand were performed using the standard non-softened potentials Default potentials for Trp84 and Trp279 side chains were maintained...
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Tài liệu Alzheimer’s Disease and Other Dementias doc
... Alzheimer’s Disease and Other Dementias Psychological Disorders Addiction Alzheimer’s Disease and Other Dementias Anxiety Disorders Child Abuse and Stress Disorders Depression and Bipolar Disorder ... brain controls our feelings, fears, and emotions; our ability to learn and store new information; and how well we recall old information The brain does all this, and more, by building, during development, ... brain architecture and function, and the diseases that affect this bond, are neuroscientists Those who study and treat the disorders that are caused by changes in brain architecture and chemistry...
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Memory performance in healthy elderly without Alzheimer’s disease: effects of time and apolipoprotein-E pptx
... visuospatial and tests of reasoning were the main contributors These included the Rosen Drawing Test [45], matching and recognition components of the Benton Visual Retention Test [4] and the Identities and ... Marder K, Bell K, Gurland B, Lantigua R, Andrews H, Feng L, Tycko B, Mayeux R 1998 The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics [see ... neurological, and neuropsychological evaluations [41,58] Past medical history was recorded with specific attention to stroke, trauma, medications, and recreational drug use All subjects underwent a standardized...
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LifeOut of Focus Alzheimer’s Disease and Related Disorders ppt
... successful, and well respected in her community At home, she and her husband especially enjoyed spending time with their six grandchildren There, Helen could put numbers and finances and tax forms ... family and friends There are individual volumes on reading disorders, attention deficit and disruptive behavior disorders, and dementia—all of these are related to our abilities to learn and integrate ... the better we can help the victims of Alzheimer’s disease and those who live with and care for them THE END OF A CAREER Helen and her husband were looking forward to retirement Helen, 56, was a...
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PET in the Evaluation of Alzheimer’s Disease and Related Disorders docx
... respectively; and my family—my wife Wei, our kids, our parents Donna and Robert and Pei and Robert, and my sibs Anne, Beth, and Mikhael, whose contributions of friendship, love, understanding of ... patients and asking questions to gather information about a patient’s behavior and appearance, ambulation and movement, mood and affect, speech, thought processes and content, insight and judgment, and ... disinhibition, and wandering in middle and late stages Such behaviors are the most troubling to caregivers, make home management difficult, and frequently lead to family distress and nursing home...
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Báo cáo khoa học: The modulation of metal bio-availability as a therapeutic strategy for the treatment of Alzheimer’s disease pptx
... and that the mechanisms of toxicity precede Ab aggregation and accumulation Curtain et al [49,65] demonstrated that the capacity for Ab to bind Zn and Cu determined its ability to penetrate and ... stress (described above), and several lines of evidence indicate that intracellular Cu deficiency in AD may involve Ab and APP Ab and its precursor APP both bind Cu, and over-expression of a C-terminal ... tight control of metals within the cell [5,6] The toxic effects of Fe and Cu and their role in numerous neurodegenerative and age-related diseases have been reviewed recently [7] Equally detrimental...
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Báo cáo khoa học: Therapeutic approaches for prion and Alzheimer’s diseases pot
... degradation and toxic to neurons Neurological symptoms in AD and prion disease are directly related to loss of neurons and synaptic connections Oligomeric and fibrillar Ab can be directly neurotoxic and ... in Great Britain, 21 in France, four in Ireland, three in the USA, two in the Netherlands and one each in Italy, Canada, Japan, Saudi Arabia, Portugal and Spain Most of the patients from these ... immunogenicity and solubility of the peptide AD Tg mice vaccinated with this peptide produced mainly an IgM class antibodies and low or absent IgG titer These animals showed behavioral improvement and a...
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