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Tau phosphorylation

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https://www.readbyqxmd.com/read/28319892/mitochondrial-hyperpolarization-in-ipsc-derived-neurons-from-patients-of-ftdp-17-with-10-16-mapt-mutation-leads-to-oxidative-stress-and-neurodegeneration
#1
Noemí Esteras, Jonathan D Rohrer, John Hardy, Selina Wray, Andrey Y Abramov
Tau protein inclusions are a frequent hallmark of a variety of neurodegenerative disorders. The 10+16 intronic mutation in MAPT gene, encoding tau, causes frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), by altering the splicing of the gene and inducing an increase in the production of 4R tau isoforms, which are more prone to aggregation. However, the molecular mechanisms linking increased 4R tau to neurodegeneration are not well understood. Here, we have used iPSC-derived neurons from patients of FTDP-17 carrying the 10+16 mutation to study the molecular mechanisms underlying neurodegeneration...
March 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28317649/clinical-validity-of-cerebrospinal-fluid-a%C3%AE-42-tau-and-phospho-tau-as-biomarkers-for-alzheimer-s-disease-in-the-context-of-a-structured-5-phase-development-framework
#2
REVIEW
Niklas Mattsson, Anders Lönneborg, Marina Boccardi, Kaj Blennow, Oskar Hansson
Novel diagnostic criteria for Alzheimer's disease (AD) incorporate biomarkers, but their maturity for implementation in clinical practice at the prodromal stage (mild cognitive impairment [MCI]) is unclear. Here, we evaluate cerebrospinal fluid (CSF) β-amyloid42 (Aβ42), total tau, and phosphorylated tau in the light of a 5-phase framework for biomarker development. Ample evidence is available for phase 1 (identifying useful leads) and phase 2 (assessing the accuracy for AD dementia versus controls) for CSF biomarkers...
April 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28317487/impact-of-cytokines-and-chemokines-on-alzheimer-s-disease-neuropathological-hallmarks
#3
Catarina Domingues, Odete A B da Cruz E Silva, Ana Gabriela Henriques
Alzheimer's disease (AD) is the most common neurodegenerative disorder, neuropathologically characterized by aggregates of β-amyloid peptides, which deposit as senile plaques, and of TAU protein, which forms neurofibrillary tangles. It is now widely accepted that neuroinflammation is implicated in AD pathogenesis. Indeed, inflammatory mediators, such as cytokines and chemokines (chemotactic cytokines) can impact on the Alzheimer´s amyloid precursor protein by affecting its expression levels and amyloidogenic processing and/or β-amyloid aggregation...
March 17, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28298292/cellular-cholesterol-homeostasis-in-alzheimer-s-disease
#4
Ta Yuan Chang, Yoshio Yamauchi, Mazahir Hasan, Catherine Cy Chang
Alzheimer's disease [AD] is the most common form of dementia in older adults. Currently, there is no cure for AD. The hallmark of AD is the accumulation of extracellular amyloid plaques composed of amyloid beta peptides [Abeta; especially Abeta1-42], and neurofibrillary tangles, composed of hyper-phosphorylated tau, accompanied with chronic neuroinflammation. Abeta are derived from the amyloid precursor protein APP. The oligomeric form of Abeta is probably the most neurotoxic species; its accumulation eventually forms the insoluble and aggregated amyloid plaques...
March 15, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28294523/flavonoids-from-potentilla-parvifolia-fisch-and-their-neuroprotective-effects-in-human-neuroblastoma-sh-sy5y-cells-in-vitro
#5
Zhenzhen Yuan, Guangxiang Luan, Zhenhua Wang, Xueyan Hao, Ji Li, Yourui Suo, Gang Li, Honglun Wang
Potentilla parvifolia Fisch. (Rosaceae) is a traditional medicinal plant in China. In this study, seven flavonoids, ayanin (1), tricin (2), quercetin (3), tiliroside (4), miquelianin (5), isoquercitrin (6), and astragalin (7), were separated and purified from ethanol extractive fractions from ethanol extracts of P. parvifolia using a combination of sevaral chromatographic methods. The human neuroblastoma SH-SY5Y cells were differentiated with all trans-retinoic acid and treated with okadaic acid to induce tau protein phosphorylation and synaptic atrophy, which could establish an Alzheimer's disease cell model...
March 11, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28285155/grape-powder-consumption-affects-the-expression-of-neurodegeneration-related-brain-proteins-in-rats-chronically-fed-a-high-fructose-high-fat-diet
#6
Hsiang Liao, Liang-Mao Chou, Yi-Wen Chien, Chi-Hao Wu, Jung-Su Chang, Ching-I Lin, Shyh-Hsiang Lin
Abnormal glucose metabolism in the brain is recognized to be associated with cognitive decline. Because grapes are rich in polyphenols that produce antioxidative and blood sugar-lowering effects, we investigated how grape consumption affects the expression and/or phosphorylation of neurodegeneration-related brain proteins in aged rats fed a high-fructose-high-fat (HFHF) diet. Wistar rats were maintained on the HFHF diet from the age of 8 weeks to 66 weeks, and then on an HFHF diet containing either 3% or 6% grape powder as an intervention for 12 weeks...
March 2, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28280340/wheat-germ-agglutinin-conjugated-liposomes-incorporated-with-cardiolipin-to-improve-neuronal-survival-in-alzheimer-s-disease-treatment
#7
Yung-Chih Kuo, Che-Yu Lin, Jay-Shake Li, Yung-I Lou
Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with surface wheat germ agglutinin (WGA) to downregulate the phosphorylation of kinases in Alzheimer's disease (AD) therapy. Cardiolipin (CL)-conjugated LIP carrying CRM (CRM-CL/LIP) and also carrying NGF (NGF-CL/LIP) were used with AD models of SK-N-MC cells and Wistar rats after an insult with β-amyloid peptide (Aβ). We found that CRM-CL/LIP inhibited the expression of phosphorylated p38 (p-p38), phosphorylated c-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 and prevented neurodegeneration of SK-N-MC cells...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28276776/brain-injury-with-diabetes-mellitus-evidence-mechanisms-and-treatment-implications
#8
Sherifa A Hamed
Diabetes mellitus is a risk for brain injury. Brain injury is associated with acute and chronic hyperglycaemia, insulin resistance, hyperinsulinemia, diabetic ketoacidosis (DKA) and hypoglycaemic events in diabetic patients. Hyperglycemia is a cause of cognitive deterioration, low intelligent quotient, neurodegeneration, brain aging, brain atrophy and dementia. Areas covered: The current review highlights the experimental, clinical, neuroimaging and neuropathological evidence of brain injury induced by diabetes and its associated metabolic derangements...
February 22, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28269786/dietary-lycopene-supplementation-improves-cognitive-performances-in-tau-transgenic-mice-expressing-p301l-mutation-via-inhibiting-oxidative-stress-and-tau-hyperphosphorylation
#9
Lixia Yu, Weiguang Wang, Wei Pang, Zhonghai Xiao, Yugang Jiang, Yan Hong
BACKGROUND: Oxidative stress is implicated in the pathogenesis of Alzheimer's disease (AD) and other tauopathies and participates in their development by promoting hyperphosphorylation of microtubule-associated protein tau. Lycopene, as an effective antioxidant, combined with vitamin E seemed to be additive against oxidative stress. OBJECTIVE: The present study was undertaken to examine whether lycopene or lycopene/vitamin E could exert protective effects on memory deficit and oxidative stress in tau transgenic mice expressing P301L mutation...
February 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28269784/a-novel-psen1-k311r-mutation-discovered-in-chinese-families-with-late-onset-alzheimer-s-disease-affects-amyloid-%C3%AE-production-and-tau-phosphorylation
#10
Jing Dong, Wei Qin, Cuibai Wei, Yi Tang, Qi Wang, Jianping Jia
BACKGROUND: Presenilin-1 (PSEN1) is the most frequently mutated gene in familial Alzheimer's disease (AD), whereas only several novel mutations have been reported in China and functional studies were seldom conducted. OBJECTIVE: We describe a novel PSEN1 K311R mutation in two Chinese families with late-onset AD and its functional impact on amyloid-β protein precursor (AβPP) processing and tau phosphorylation. METHODS: The mutation was detected by direct sequencing of PSEN1 exon 9...
February 28, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28268049/application-of-an-esi-qtof-method-for-the-detailed-characterization-of-gsk-3%C3%AE-inhibitors
#11
Angela De Simone, Jessica Fiori, Marina Naldi, Annalisa D'Urzo, Vincenzo Tumiatti, Andrea Milelli, Vincenza Andrisano
The crucial role of Glycogen Synthase Kinase 3 (GSK-3β) as a pivotal player in Alzheimer's Disease (AD) has recently inspired significant attempts to design and synthesize potent kinase inhibitors. In fact GSK-3β is considered the main kinase which catalyzes the microtubule-associated protein tau hyper-phosphorylation and the neurofibrillary tangles (NFT) in vitro and in vivo, The first classes of GSK-3β inhibitors were classified as ATP-competitive and, therefore, they lack of an efficient degree of selectivity over other kinases...
February 27, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28261965/relationship-between-cytokine-levels-in-the-cerebrospinal-fluid-and-11c-pittsburgh-compound%C3%A2-b-retention-in-patients-with-mild-cognitive-impairment
#12
Yoshitake Abe, Noriyuki Kimura, Ryuichi Takahashi, Megumi Gotou, Ken Mizukami, Hirotatsu Uchida, Etsuro Matsubara
AIM: In the present study, we examined the relationship between cytokine levels in the cerebrospinal fluid (CSF) and (11) C-Pittsburgh compound B (PiB) retention in patients with mild cognitive impairment. METHODS: A total of 33 participants (12 men and 21 women; mean age 76.5 years) with mild cognitive impairment underwent neuropsychological assessments, PiB positron emission tomography and analysis of cytokine levels in the CSF. The CSF levels of 48 cytokines and growth factors were measured using multiplex immunoassays...
March 5, 2017: Geriatrics & Gerontology International
https://www.readbyqxmd.com/read/28261874/samp8-mice-as-a-neuropathological-model-of-accelerated-brain-aging-and-dementia-toshio-takeda-s-legacy-and-future-directions
#13
REVIEW
Ichiro Akiguchi, Mercè Pallàs, Herbert Budka, Haruhiko Akiyama, Masaki Ueno, Jingxian Han, Hideo Yagi, Tomohumi Nishikawa, Yoichi Chiba, Hiroshi Sugiyama, Ryoya Takahashi, Keiko Unno, Keiichi Higuchi, Masanori Hosokawa
Senescence accelerated mice P8 (SAMP8) show significant age-related deteriorations in memory and learning ability in accordance with early onset and rapid advancement of senescence. Brains of SAMP8 mice reveal an age-associated increase of PAS-positive granular structures in the hippocampal formation and astrogliosis in the brain stem and hippocampus. A spongy degeneration in the brain stem appears at 1 month of age and reaches a maximum at 4-8 months. In addition, clusters of activated microglia also appear around the vacuoles in the brain stem...
March 6, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28258221/quantitative-mapping-of-microtubule-associated-protein-2c-map2c-phosphorylation-and-regulatory-protein-14-3-3-%C3%AE-binding-sites-reveals-key-differences-between-map2c-and-its-homolog-tau
#14
Séverine Jansen, Kateřina Melková, Zuzana Trošanová, Kateřina Hanáková, Milan Zachrdla, Jiři Nováček, Erik Župa, Zbyněk Zdráhal, Jozef Hritz, Lukáš Žídek
Microtubule associated protein 2c (MAP2c) is involved in neuronal development and is less characterized than its homolog Tau, which has various roles in neurodegeneration. Using NMR methods providing single-residue resolution and quantitative comparison, we investigated molecular interactions important for the regulatory roles of MAP2c in microtubule dynamics. We found that MAP2c and Tau significantly differ in the position and kinetics of sites that are phosphorylated by cAMP-dependent protein kinase (PKA), even in highly homologous regions...
March 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28253985/mitochondria-targeted-molecules-as-potential-drugs-to-treat-patients-with-alzheimer-s-disease
#15
A P Reddy, P H Reddy
Alzheimer's disease (AD) is the most common multifactorial mental illness affecting the elderly population in the world. Its prevalence increases as person ages. There is no known drug or agent that can delay or prevent the AD and its progression. Extensive research has revealed that multiple cellular pathways involved, including amyloid beta production, mitochondrial structural and functional changes, hyperphosphorylation of Tau and NFT formation, inflammatory responses, and neuronal loss in AD pathogenesis...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28251926/phospho-regulation-of-tau-modulates-inhibition-of-kinesin-1-motility
#16
Jamie L Stern, Dominique V Lessard, Gregory J Hoeprich, Gerardo A Morfini, Christopher L Berger
Microtubule-based axonal transport is tightly regulated by numerous pathways ensuring appropriate delivery of specific organelle cargoes to selected subcellular domains. Highlighting the importance of this process, pathological evidence has linked alterations in these pathways to the pathogenesis of several neurodegenerative diseases. An important regulator of this system, the microtubule associated protein Tau has been shown to participate in signaling cascades, modulate microtubule dynamics and preferentially inhibit kinesin-1 motility...
March 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28247064/genome-wide-association-study-identifies-four-novel-loci-associated-with-alzheimer-s-endophenotypes-and-disease-modifiers
#17
Yuetiva Deming, Zeran Li, Manav Kapoor, Oscar Harari, Jorge L Del-Aguila, Kathleen Black, David Carrell, Yefei Cai, Maria Victoria Fernandez, John Budde, Shengmei Ma, Benjamin Saef, Bill Howells, Kuan-Lin Huang, Sarah Bertelsen, Anne M Fagan, David M Holtzman, John C Morris, Sungeun Kim, Andrew J Saykin, Philip L De Jager, Marilyn Albert, Abhay Moghekar, Richard O'Brien, Matthias Riemenschneider, Ronald C Petersen, Kaj Blennow, Henrik Zetterberg, Lennart Minthon, Vivianna M Van Deerlin, Virginia Man-Yee Lee, Leslie M Shaw, John Q Trojanowski, Gerard Schellenberg, Jonathan L Haines, Richard Mayeux, Margaret A Pericak-Vance, Lindsay A Farrer, Elaine R Peskind, Ge Li, Antonio F Di Narzo, John S K Kauwe, Alison M Goate, Carlos Cruchaga
More than 20 genetic loci have been associated with risk for Alzheimer's disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case-control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS)...
February 28, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28238547/hallmarks-of-alzheimer-s-disease-in-stem-cell-derived-human-neurons-transplanted-into-mouse-brain
#18
Ira Espuny-Camacho, Amaia M Arranz, Mark Fiers, An Snellinx, Kunie Ando, Sebastian Munck, Jerome Bonnefont, Laurie Lambot, Nikky Corthout, Lorna Omodho, Elke Vanden Eynden, Enrico Radaelli, Ina Tesseur, Selina Wray, Andreas Ebneth, John Hardy, Karelle Leroy, Jean-Pierre Brion, Pierre Vanderhaeghen, Bart De Strooper
Human pluripotent stem cells (PSCs) provide a unique entry to study species-specific aspects of human disorders such as Alzheimer's disease (AD). However, in vitro culture of neurons deprives them of their natural environment. Here we transplanted human PSC-derived cortical neuronal precursors into the brain of a murine AD model. Human neurons differentiate and integrate into the brain, express 3R/4R Tau splice forms, show abnormal phosphorylation and conformational Tau changes, and undergo neurodegeneration...
February 15, 2017: Neuron
https://www.readbyqxmd.com/read/28238167/effects-of-cox1-2-5-lox-blockade-in-alzheimer-transgenic-3xtg-ad-mice
#19
Alessandra Bitto, Daniela Giuliani, Giovanni Pallio, Natasha Irrera, Eleonora Vandini, Fabrizio Canalini, Davide Zaffe, Alessandra Ottani, Letteria Minutoli, Mariagrazia Rinaldi, Salvatore Guarini, Francesco Squadrito, Domenica Altavilla
OBJECTIVE AND DESIGN: Alzheimer's disease (AD) is associated with amyloid plaques (Aβ) and hyperphosphorylated tau protein tangles in the brain. We investigated the possible neuroprotective role of flavocoxid, a dual inhibitor of cyclooxygenases-1/2 (COX-1/2) and 5-Lipoxygenase (5-LOX), in triple-transgenic (3xTg-AD) mice. SUBJECTS: Mice were 3 months at the beginning of the study. TREATMENT: Animals received once daily for 3-month saline solution or flavocoxid (20 mg/kg/ip)...
February 25, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28236445/the-heidenhain-variant-of-creutzfeldt-jakob-disease-and-concomitant-tau-pathology-a-case-report
#20
Edvard Ehler, Michael Pipka, Alena Meleková, Petra Mandysová, Silvie Johanidesová, Radoslav Matěj, Robert Rusina
The Heidenhain form of Creutzfeldt-Jakob disease (CJD) is a rare CJD variant with predominantly visual symptoms in the early stages. Clinical manifestations of metamorphopsia, hemianopia and Balint's syndrome correlate with the involvement of the posterior cortical regions. A 71-year old healthy and very active man was admitted because of impaired visual acuity, hemianopia, and gait disturbance progressing over one week. MRI found typical cortical hyperintensities in the occipital regions while rhythm slowing and sharp waves were seen in the occipital regions on EEG...
February 10, 2017: Neurologia i Neurochirurgia Polska
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