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Tau phosphorylation

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https://www.readbyqxmd.com/read/29786737/anti-amyloidogenic-properties-of-an-ethyl-acetate-fraction-from-actinidia-arguta-in-a%C3%AE-1-42-induced-icr-mice
#1
Jeong Su Ha, Jong Min Kim, Seon Kyeong Park, Jin Yong Kang, Du Sang Lee, Uk Lee, Dae-Ok Kim, Sung-Gil Choi, Ho Jin Heo
This study aimed to investigate the ameliorating effect of an ethyl acetate fraction from the fruit Actinidia arguta (EFAA) on amyloid beta (Aβ)-induced neurotoxicity and cognitive deficits in ICR mice. EFAA showed potent protective effects against Aβ-induced neurotoxicity through 2',7'-dichlorofluorescein diacetate (DCF-DA), 2',3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release into the assay medium. EFAA treatment reduced the intracellular ROS level and lactate dehydrogenase (LDH) release in the mitochondria, and increased cell viability in Aβ-induced neuroblastoma MC-IXC cells...
May 22, 2018: Food & Function
https://www.readbyqxmd.com/read/29782321/pyk2-is-a-novel-tau-tyrosine-kinase-that-is-regulated-by-the-tyrosine-kinase-fyn
#2
Chuanzhou Li, Jürgen Götz
The protein tyrosine kinase Pyk2 is encoded by PTK2B, a novel Alzheimer's disease (AD) susceptibility variant, with the PTK2B risk allele being associated with increased mRNA levels, suggestive of increased Pyk2 levels. However, the role of Pyk2, a member of the focal adhesion kinase (FAK) family, in AD pathology and its regulation are largely unknown. To address this, we generated mice with neuronal expression of human Pyk2. Because we had previously reported an association of Pyk2 and hyperphosphorylated tau (a hallmark feature of AD) in human tau transgenic pR5 mice, we also generated Pyk2/tau double-transgenic mice, which exhibit increased tyrosine phosphorylation and accumulation of tau...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29781013/design-and-synthesis-of-aza-indolyl-maleimide-based-covalent-inhibitors-of-glycogen-synthase-kinase-3%C3%AE
#3
Zhimin Yang, Hui Liu, Botao Pan, Fengli He, Zhengying Pan
As an important kinase in multiple signal transduction pathways, GSK-3β has been an attractive target for chemical probe discovery and drug development. Compared to numerous reversible inhibitors that have been developed, covalent inhibitors of GSK-3β are noticeably lacking. Here, we report the discovery of a series of covalent GSK-3β inhibitors by optimizing both non-covalent interactions and reactive groups. Among these covalent inhibitors, compound 38b with a mild α-fluoromethyl amide reactive group emerges as a selective and covalent inhibitor against GSK-3β, effectively inhibits the phosphorylation of glycogen synthase and tau protein, and increases β-catenin's levels in living cells...
May 21, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29776428/evidence-of-the-impact-of-systemic-inflammation-on-neuroinflammation-from-a-non-bacterial-endotoxin-animal-model
#4
Chunxia Huang, Michael Garnet Irwin, Gordon Tin Chun Wong, Raymond Chuen Chung Chang
BACKGROUND: Systemic inflammation induces neuroinflammation and cellular changes such as tau phosphorylation to impair cognitive function, including learning and memory. This study uses a single model, laparotomy without any pathogen, to characterize these changes and their responses to anti-inflammatory treatment in the intermediate term. METHODS: In a two-part experiment, wild-type C57BL/6N mice (male, 3 month old, 25 ± 2 g) were subjected to sevoflurane anesthesia alone or to a laparotomy...
May 17, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29774334/a-comparative-study-of-epa-enriched-ethanolamine-plasmalogen-and-epa-enriched-phosphatidylethanolamine-on-a%C3%AE-42-induced-cognitive-deficiency-in-a-rat-model-of-alzheimer-s-disease
#5
Hongxia Che, Qian Li, Tiantian Zhang, Lin Ding, Lingyu Zhang, Haohao Shi, Teruyoshi Yanagita, Changhu Xue, Yaoguang Chang, Yuming Wang
Ethanolamine plasmalogen (pPE), a major phospholipid in neuronal membranes, is specifically reduced in postmortem brains from patients with Alzheimer's disease (AD). The purpose of the present study was to compare the effects of EPA-enriched ethanolamine plasmalogen (EPA-pPE) and EPA-enriched phosphatidylethanolamine (EPA-PE) on cognitive deficiency and illustrate the possible underlying mechanisms. SD rats were divided into four groups including the sham group injected with 0.9% saline and three amyloid-β (Aβ) infusion groups, Aβ42 group, EPA-pPE group and EPA-PE group...
May 18, 2018: Food & Function
https://www.readbyqxmd.com/read/29772805/ethyl-acetate-fraction-from-persimmon-diospyros-kaki-ameliorates-cerebral-neuronal-loss-and-cognitive-deficit-via-the-jnk-akt-pathway-in-tmt-induced-mice
#6
Jong Min Kim, Seon Kyeong Park, Jin Yong Kang, Su Bin Park, Seul Ki Yoo, Hye Ju Han, Chul-Woo Kim, Uk Lee, Sea-Hyun Kim, Ho Jin Heo
This study was conducted to assess the antioxidant capacity and protective effect of the ethyl acetate fraction from persimmon ( Diospyros kaki ) (EFDK) on H₂O₂-induced hippocampal HT22 cells and trimethyltin chloride (TMT)-induced Institute of Cancer Research (ICR) mice. EFDK had high antioxidant activities and neuroprotective effects in HT22 cells. EFDK ameliorated behavioral and memory deficits in Y-maze, passive avoidance and Morris water maze tests. Also, EFDK restored the antioxidant system by regulating malondialdehyde (MDA), superoxide dismutase (SOD) and reduced gluthathione (GSH), and the cholinergic system by controlling the acetylcholine (ACh) level and acetylcholinesterase (AChE) activity and expression...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29760662/targeting-renin-angiotensin-system-against-alzheimer-s-disease
#7
REVIEW
Abadi Kahsu Gebre, Birhanetensay Masresha Altaye, Tesfay Mehari Atey, Kald Beshir Tuem, Derbew Fikadu Berhe
Renin Angiotensin System (RAS) is a hormonal system that regulates blood pressure and fluid balance through a coordinated action of renal, cardiovascular, and central nervous systems. In addition to its hemodynamic regulatory role, RAS involves in many brain activities, including memory acquisition and consolidation. This review has summarized the involvement of RAS in the pathology of Alzheimer's disease (AD), and the outcomes of treatment with RAS inhibitors. We have discussed the effect of brain RAS in the amyloid plaque (Aβ) deposition, oxidative stress, neuroinflammation, and vascular pathology which are directly and indirectly associated with AD...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29760653/ck2-phosphorylating-i-2-pp2a-set-mediates-tau-pathology-and-cognitive-impairment
#8
Qing Zhang, Yiyuan Xia, Yongjun Wang, Yangping Shentu, Kuan Zeng, Yacoubou A R Mahaman, Fang Huang, Mengjuan Wu, Dan Ke, Qun Wang, Bin Zhang, Rong Liu, Jian-Zhi Wang, Keqiang Ye, Xiaochuan Wang
Casein kinase 2 (CK2) is highly activated in Alzheimer disease (AD) and is associated with neurofibrillary tangles formation. Phosphorylated SET, a potent PP2A inhibitor, mediates tau hyperphosphorylation in AD. However, whether CK2 phosphorylates SET and regulates tau pathological phosphorylation in AD remains unclear. Here, we show that CK2 phosphorylating SET at Ser9 induced tau hyperphosphorylation in AD. We found that either Aβ treatment or tau overexpression stimulated CK2 activation leading to SET Ser9 hyperphosphorylation in neurons and animal models, while inhibition of CK2 by TBB abolished this event...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29758943/novel-key-players-in-the-development-of-tau-neuropathology-focus-on-the-5-lipoxygenase
#9
Elisabetta Lauretti, Domenico Praticò
Tauopathies belong to a large group of neurodegenerative diseases characterized by progressive accumulation of hyperphosphorylated tau. Tau is a microtubule binding protein which is necessary for their assembly and stability. However, tau affinity for microtubules mainly depends on its phosphorylation status, which is the result of a delicate balance between kinases and phosphatases activity. Any significant changes in this equilibrium can promote tau fibrillation, aggregation, neuronal dysfunction, and ultimately neuronal loss...
May 11, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29750243/c9orf72-dipeptide-repeat-poly-ga-inclusions-promote-intracellular-aggregation-of-phosphorylated-tdp-43
#10
Takashi Nonaka, Masami Masuda-Suzukake, Masato Hosokawa, Aki Shimozawa, Shinobu Hirai, Haruo Okado, Masato Hasegawa
Amyotrophic lateral sclerosis and frontotemporal lobar degeneration are neurodegenerative diseases characterized by accumulation of insoluble aggregates of phosphorylated 43-kDa TAR DNA-binding protein (TDP-43), and linked with abnormal expansion of a hexanucleotide repeat in an intron of chromosome 9 open reading frame 72 (C9ORF72). However, the relationship between C9ORF72 mutations and TDP-43 aggregation remains unknown. Non-ATG-dependent translation of C9ORF72 repeats produces dipeptide repeat (DPR) proteins, which form p62-positive aggregates in cerebral cortex and cerebellum of patients...
May 10, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29748322/near-atomic-model-of-microtubule-tau-interactions
#11
Elizabeth H Kellogg, Nisreen M A Hejab, Simon Poepsel, Kenneth H Downing, Frank DiMaio, Eva Nogales
Tau is a developmentally regulated axonal protein that stabilizes and bundles microtubules (MTs). Its hyperphosphorylation is thought to cause detachment from MTs and subsequent aggregation into fibrils implicated in Alzheimer's disease. It is unclear which tau residues are crucial for tau-MT interactions, where tau binds on MTs, and how it stabilizes them. We used cryo-electron microscopy to visualize different tau constructs on MTs, and computational approaches to generate atomic models of tau-tubulin interactions...
May 10, 2018: Science
https://www.readbyqxmd.com/read/29746089/physiological-a%C3%AE-concentrations-produce-a-more-biomimetic-representation-of-the-alzheimer-s-disease-phenotype-in-ipsc-derived-human-neurons
#12
Bonnie J Berry, Alec S T Smith, Christopher J Long, Candace C Martin, James J Hickman
Alzheimer's disease (AD) is characterized by slow, progressive neurodegeneration leading to severe neurological impairment, but current drug development efforts are limited by the lack of robust, human-based disease models. Amyloid-β (Aβ) is known to play an integral role in AD progression as it has been shown to interfere with neurological function. However, studies into AD pathology commonly apply Aβ to neurons for short durations at non-physiological concentrations to induce an exaggerated dysfunctional phenotype...
May 10, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29741516/the-influence-of-anesthetics-on-substantia-nigra-tyrosine-hydroxylase-expression-and-tau-phosphorylation-in-the-hypoxic-ischemic-near-term-lamb
#13
Melinda Barkhuizen, Fleur J P van Dijck, Reint K Jellema, Ruth Gussenhoven, Imke Engelbertink, Ralph van Mechelen, Jack P M Cleutjens, Matthias Seehase, Harry W M Steinbusch, Luc J Zimmermann, A W Danilo Gavilanes, Boris W Kramer
BackgroundGeneral anesthetics could protect key neurotransmitter systems, such as the dopaminergic system, from hypoxic-ischemic encephalopathy (HIE) by limiting excessive glutamatergic neurotransmission. However, anesthetics may adversely affect inflammation and tau phosphorylation.MethodsA near-term sheep model of HIE by umbilical cord occlusion (UCO) under anesthesia was used. The effect of propofol and isoflurane on the dopaminergic neurotransmitter phenotype in the substantia nigra (SN) was studied using tyrosine hydroxylase immunohistochemistry...
May 9, 2018: Pediatric Research
https://www.readbyqxmd.com/read/29740275/synaptic-tau-seeding-precedes-tau-pathology-in-human-alzheimer-s-disease-brain
#14
Sarah L DeVos, Bianca T Corjuc, Derek H Oakley, Chloe K Nobuhara, Riley N Bannon, Alison Chase, Caitlin Commins, Jose A Gonzalez, Patrick M Dooley, Matthew P Frosch, Bradley T Hyman
Alzheimer's disease (AD) is defined by the presence of intraneuronal neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau aggregates as well as extracellular amyloid-beta plaques. The presence and spread of tau pathology through the brain is classified by Braak stages and thought to correlate with the progression of AD. Several in vitro and in vivo studies have examined the ability of tau pathology to move from one neuron to the next, suggesting a "prion-like" spread of tau aggregates may be an underlying cause of Braak tau staging in AD...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29738850/intermittent-streptozotocin-administration-induces-behavioral-and-pathological-features-relevant-to-alzheimer-s-disease-and-vascular-dementia
#15
Andrew S Murtishaw, Chelcie F Heaney, Monica M Bolton, Krystal Courtney D Belmonte, Michael A Langhardt, Jefferson W Kinney
RATIONALE: Diabetes mellitus (DM) is a major risk factor for Alzheimer's disease and vascular dementia. Few animal models exist that focus on the metabolic contributions to dementia onset and progression. Thus, there is strong scientific rationale to explore the effects of streptozotocin (STZ), a diabetogenic compound, on vascular and inflammatory changes within the brain. OBJECTIVE AND METHODS: The present study was designed to evaluate the effect of staggered, low-dose administration of STZ on behavioral and cognitive deficits, neuroinflammation, tau pathology, and histopathological alterations related to dementia...
May 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29732953/suppressive-effects-of-the-peel-of-citrus-kawachiensis-kawachi-bankan-on-astroglial-activation-tau-phosphorylation-and-inhibition-of-neurogenesis-in-the-hippocampus-of-type-2-diabetic-db-db-mice
#16
Satoshi Okuyama, Wakana Shinoka, Kumi Nakamura, Maho Kotani, Atsushi Sawamoto, Kuniaki Sugawara, Masahiko Sudo, Mitsunari Nakajima, Yoshiko Furukawa
We previously reported that the dried peel powder of Citrus kawachiensis exerted anti-inflammatory effects in the brain in several animal models. Hyperglycemia induces inflammation and oxidative stress and causes massive damage in the brain; therefore, we herein examined the anti-inflammatory and other effects of the dried peel powder of C. kawachiensis in the streptozotocin-induced hyperglycemia mice model and in the type 2 diabetic db/db mice model. The C. kawachiensis administration inhibited microglial activation in the hippocampus in the streptozotocin-injected mice...
May 6, 2018: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29731706/phosphorylation-of-threonine-175-tau-in-the-induction-of-tau-pathology-in-amyotrophic-lateral-sclerosis-frontotemporal-spectrum-disorder-als-ftsd-a-review
#17
REVIEW
Alexander J Moszczynski, Matthew A Hintermayer, Michael J Strong
Approximately 50-60% of all patients with amyotrophic lateral sclerosis (ALS) will develop a deficit of frontotemporal function, ranging from frontotemporal dementia (FTD) to one or more deficits of neuropsychological, speech or language function which are collectively known as the frontotemporal spectrum disorders of ALS (ALS-FTSD). While the neuropathology underlying these disorders is most consistent with a widespread alteration in the metabolism of transactive response DNA-binding protein 43 (TDP-43), in both ALS with cognitive impairment (ALSci) and ALS with FTD (ALS-FTD; also known as MND-FTD) there is evidence for alterations in the metabolism of the microtubule associated protein tau...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29730992/a-new-tao-kinase-inhibitor-reduces-tau-phosphorylation-at-sites-associated-with-neurodegeneration-in-human-tauopathies
#18
Caterina Giacomini, Chuay-Yeng Koo, Natalia Yankova, Ignatius A Tavares, Selina Wray, Wendy Noble, Diane P Hanger, Jonathan D H Morris
In Alzheimer's disease (AD) and related tauopathies, the microtubule-associated protein tau is highly phosphorylated and aggregates to form neurofibrillary tangles that are characteristic of these neurodegenerative diseases. Our previous work has demonstrated that the thousand-and-one amino acid kinases (TAOKs) 1 and 2 phosphorylate tau on more than 40 residues in vitro. Here we show that TAOKs are phosphorylated and active in AD brain sections displaying mild (Braak stage II), intermediate (Braak stage IV) and advanced (Braak stage VI) tau pathology and that active TAOKs co-localise with both pre-tangle and tangle structures...
May 7, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29729307/virgin-coconut-oil-vco-by-normalizing-nlrp3-inflammasome-showed-potential-neuroprotective-effects-in-amyloid-%C3%AE-induced-toxicity-and-high-fat-diet-fed-rat
#19
Fatemeh Mirzaei, Mozafar Khazaei, Alireza Komaki, Iraj Amiri, Cyrus Jalili
Both dyslipidemia and Alzheimer disease (AD) are associated with aging. In this study, the effects of virgin coconut oil (VCO) on inflammasome and oxidative stress in Alzheimer's model (receiving Amyloid-β (Aβ)) and high-fat diet (HFD) model were determined. A total of 120 male Wistar rats, were divided into 12 groups (n = 10), including; healthy control, sham surgery, sham surgery receiving normal saline, HFD, HFD + 8% VCO, HFD + 10% VCO, Aβ received rats, Aβ + 8%VCO, Aβ + 10%VCO, HFD + Aβ, HFD + Aβ+8%VCO, and HFD + Aβ + 10%VCO...
May 2, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29728702/elevated-levels-of-brain-homocysteine-directly-modulate-the-pathological-phenotype-of-a-mouse-model-of-tauopathy
#20
Antonio Di Meco, Jian-Guo Li, Carlos Barrero, Salim Merali, Domenico Praticò
A high circulating level of homocysteine (Hcy), also known as hyperhomocysteinemia, is a risk factor for Alzheimer's disease (AD). Previous studies show that elevated Hcy promotes brain amyloidosis and behavioral deficits in mouse models of AD. However, whether it directly modulates the development of tau neuropathology independently of amyloid beta in vivo is unknown. Herein, we investigate the effect of diet-induced elevated levels of brain Hcy on the phenotype of a relevant mouse model of human tauopathy...
May 4, 2018: Molecular Psychiatry
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