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https://www.readbyqxmd.com/read/29154274/cognitive-decline-in-preclinical-alzheimer-s-disease-amyloid-beta-versus-tauopathy
#1
Colin M Huber, Connor Yee, Taylor May, Apoorva Dhanala, Cassie S Mitchell
 We perform a large-scale meta-analysis of 51 peer-reviewed 3xTg-AD mouse publications to compare Alzheimer's disease (AD) quantitative clinical outcome measures, including amyloid-β (Aβ), total tau, and phosphorylated tau (pTau), with cognitive performance in Morris water maze (MWM) and Novel Object Recognition (NOR). "High" levels of Aβ (Aβ40, Aβ42) showed significant but weak trends with cognitive decline (MWM: slope = 0.336, R2 = 0.149, n = 259, p < 0.001; NOR: slope = 0.156, R2 = 0...
November 14, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29133432/locus-coeruleus-ablation-exacerbates-cognitive-deficits-neuropathology-and-lethality-in-p301s-tau-transgenic-mice
#2
Termpanit Chalermpalanupap, Jason P Schroeder, Jacki M Rorabaugh, L Cameron Liles, James J Lah, Allan I Levey, David Weinshenker
The brainstem locus coeruleus (LC) supplies norepinephrine (NE) to the forebrain and degenerates in Alzheimer's disease (AD). Loss of LC neurons is correlated with increased severity of other AD hallmarks including β-amyloid (Aβ) plaques, tau neurofibrillary tangles and cognitive deficits, suggesting that it contributes to the disease progression. Lesions of the LC in amyloid-based transgenic mouse models of AD exacerbate Aβ pathology, neuroinflammation, and cognitive deficits, but it is unknown how the loss of LC neurons affects tau-mediated pathology or behavioral abnormalities...
November 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29128902/overexpression-of-5-lipoxygenase-worsens-the-phenotype-of-a-mouse-model-of-tauopathy
#3
Phillip F Giannopoulos, Domenico Praticò
Brain accumulation of increasing amount of phosphorylated microtubule associated tau protein is one the major hallmark lesions of Alzheimer's disease (AD) and related tauopathies. Consistent evidence from clinical and animal studies has shown that neuroinflammation characterizes these diseases. The 5-lipoxygenase (5LO) is an enzyme protein whose metabolic products are lipids with potent inflammatory actions. Previously, we showed that blockade of 5LO activation ameliorates the phenotype of the htau transgenic mice...
November 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29126071/%C3%AE-lipoic-acid-improves-abnormal-behavior-by-mitigation-of-oxidative-stress-inflammation-ferroptosis-and-tauopathy-in-p301s-tau-transgenic-mice
#4
Yan-Hui Zhang, Da-Wei Wang, Shuang-Feng Xu, Shuai Zhang, Yong-Gang Fan, Ying-Ying Yang, Shi-Qi Guo, Shan Wang, Tian Guo, Zhan-You Wang, Chuang Guo
Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by neurofibrillary tangles (NFTs) composed of Tau protein. α-Lipoic acid (LA) has been found to stabilize the cognitive function of AD patients, and animal study findings have confirmed its anti-amyloidogenic properties. However, the underlying mechanisms remain unclear, especially with respect to the ability of LA to control Tau pathology and neuronal damage. Here, we found that LA supplementation effectively inhibited the hyperphosphorylation of Tau at several AD-related sites, accompanied by reduced cognitive decline in P301S Tau transgenic mice...
November 7, 2017: Redox Biology
https://www.readbyqxmd.com/read/29121589/pharmacological-targeting-of-gsk-3-and-nrf2-provides-neuroprotection-in-a-preclinical-model-of-tauopathy
#5
Antonio Cuadrado, Sebastian Kügler, Isabel Lastres-Becker
Tauopathies are a group of neurodegenerative disorders where TAU protein is presented as aggregates or is abnormally phosphorylated, leading to alterations of axonal transport, neuronal death and neuroinflammation. Currently, there is no treatment to slow progression of these diseases. Here, we have investigated whether dimethyl fumarate (DMF), an inducer of the transcription factor NRF2, could mitigate tauopathy in a mouse model. The signaling pathways modulated by DMF were also studied in mouse embryonic fibroblast (MEFs) from wild type or KEAP1-deficient mice...
November 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/29121398/protein-phosphatase-2a-and-tau-an-orchestrated-pas-de-deux
#6
REVIEW
Goce Taleski, Estelle Sontag
The neuronal microtubule-associated protein tau serves a critical role in regulating axonal microtubule dynamics to support neuronal and synaptic functions. Furthermore, it contributes to glutamatergic regulation and synaptic plasticity. Emerging evidence also suggests that tau serves as a signaling scaffold. Tau function and subcellular localisation are tightly regulated, in part, by the orchestrated interplay between phosphorylation and dephosphorylation events. Significantly, protein phosphatase type 2A (PP2A), encompassing the regulatory PPP2R2A (or Bα) subunit, is a major brain heterotrimeric enzyme and the primary tau Ser/Thr phosphatase in vivo...
November 9, 2017: FEBS Letters
https://www.readbyqxmd.com/read/29110782/biomarkers-in-cerebrospinal-fluid-for-synucleinopathies-tauopathies-and-other-neurodegenerative-disorders
#7
Tainá M Marques, Anouke Van Rumund, H Bea Kuiperij, Marcel M Verbeek
The incidence of neurodegenerative disorders is increasing due to worldwide population aging. In general, sporadic forms account for 90% of total cases with neurodegenerative disorders and the reasons underlying initiation or progression of these diseases remain unknown for almost all disorders. To date, diagnosis is mainly based on clinical symptoms and neuroimaging, which is in many cases insufficient due to overlap in clinical symptoms among several neurodegenerative disorders. Therefore, postmortem neuropathologic confirmation remains the gold-standard diagnostic technique for many disorders...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29107053/conserved-brain-myelination-networks-are-altered-in-alzheimer-s-and-other-neurodegenerative-diseases
#8
Mariet Allen, Xue Wang, Jeremy D Burgess, Jens Watzlawik, Daniel J Serie, Curtis S Younkin, Thuy Nguyen, Kimberly G Malphrus, Sarah Lincoln, Minerva M Carrasquillo, Charlotte Ho, Paramita Chakrabarty, Samantha Strickland, Melissa E Murray, Vivek Swarup, Daniel H Geschwind, Nicholas T Seyfried, Eric B Dammer, James J Lah, Allan I Levey, Todd E Golde, Cory Funk, Hongdong Li, Nathan D Price, Ronald C Petersen, Neill R Graff-Radford, Steven G Younkin, Dennis W Dickson, Julia R Crook, Yan W Asmann, Nilüfer Ertekin-Taner
INTRODUCTION: Comparative transcriptome analyses in Alzheimer's disease (AD) and other neurodegenerative proteinopathies can uncover both shared and distinct disease pathways. METHODS: We analyzed 940 brain transcriptomes including patients with AD, progressive supranuclear palsy (PSP; a primary tauopathy), and control subjects. RESULTS: We identified transcriptional coexpression networks implicated in myelination, which were lower in PSP temporal cortex (TCX) compared with AD...
October 26, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29106033/brain-5-lipoxygenase-over-expression-worsens-memory-synaptic-integrity-and-tau-pathology-in-the-p301s-mice
#9
Alana N Vagnozzi, Phillip F Giannopoulos, Domenico Praticò
Progressive accumulation of highly phosphorylated tau protein isoforms is the main feature of a group of neurodegenerative diseases collectively called tauopathies. Data from human and animal models of these diseases have shown that neuroinflammation often accompanies their pathogenesis. The 5-lipoxygenase (5LO) is an enzyme widely expressed in the brain and a source of potent pro-inflammatory mediators, while its pharmacological inhibition modulates the phenotype of a tau transgenic mouse model, the htau mice...
November 4, 2017: Aging Cell
https://www.readbyqxmd.com/read/29105391/the-molecular-chaperone-artemin-efficiently-blocks-fibrillization-of-tau-protein-in-vitro
#10
Zahra Khosravi, Mohammad Ali Nasiri Khalili, Sharif Moradi, Reza Hassan Sajedi, Mehdi Zeinoddini
OBJECTIVES: Aggregation of the TAU proteins in the form of neurofibrillary tangles (NFTs) in the brain is a common risk factor in tauopathies including Alzheimer's disease (AD). Several strategies have been implemented to target NFTs, among which chaperones, which facilitate the proper folding of proteins, appear to hold great promise in effectively inhibiting TAU polymerization. The aim of this study was to analyze the impact of the chaperone Artemin on TAU aggregation in vitro. MATERIALS AND METHODS: In this experimental study, recombinant TAU- or Artemin proteins were expressed in E...
January 2018: Cell Journal
https://www.readbyqxmd.com/read/29103039/the-need-to-separate-chronic-traumatic-encephalopathy-neuropathology-from-clinical-features
#11
Grant L Iverson, C Dirk Keene, George Perry, Rudolph J Castellani
There is tremendous recent interest in chronic traumatic encephalopathy (CTE) in former collision sport athletes, civilians, and military veterans. This critical review places important recent research results into a historical context. In 2015, preliminary consensus criteria were developed for defining the neuropathology of CTE, which substantially narrowed the pathology previously reported to be characteristic. There are no agreed upon clinical criteria for diagnosis, although sets of criteria have been proposed for research purposes...
October 30, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29101031/a-deficiency-of-the-glun2c-subunit-of-the-n-methyl-d-aspartate-receptor-is-neuroprotective-in-a-mouse-model-of-ischemic-stroke
#12
Adam Holmes, Ning Zhou, Deborah L Donahue, Rashna Balsara, Francis J Castellino
The N-methyl-d-aspartate receptor (NMDAR) ion channel plays a pivotal role in the pathology of ischemic stroke. The functional receptor consists of two GluN1 subunits (a-h) and two GluN2 subunits (A/B/C/D), the expression of which are spatially and temporally regulated in pathological and physiological conditions. While the role of the GluN2A and GluN2B subunit in ischemic stroke has been well developed, the role of the GluN2C subunit in ischemia is not well understood. Following middle carotid artery occlusion (MCAO), GluN2C(-/-) male mice displayed similar volumes of infarct as wild-type (WT) mice...
October 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29096320/mitochondrial-dysfunction-in-parkinsonian-mesenchymal-stem-cells-impairs-differentiation
#13
Plamena R Angelova, Mario Barilani, Christopher Lovejoy, Marta Dossena, Mariele Viganò, Agostino Seresini, Daniela Piga, Sonia Gandhi, Gianni Pezzoli, Andrey Y Abramov, Lorenza Lazzari
Sporadic cases account for 90-95% of all patients with Parkinson's Disease (PD). Atypical Parkinsonism comprises approximately 20% of all patients with parkinsonism. Progressive Supranuclear Palsy (PSP) belongs to the atypical parkinsonian diseases and is histopathologically classified as a tauopathy. Here, we report that mesenchymal stem cells (MSCs) derived from the bone marrow of patients with PSP exhibit mitochondrial dysfunction in the form of decreased membrane potential and inhibited NADH-dependent respiration...
October 20, 2017: Redox Biology
https://www.readbyqxmd.com/read/29089864/axonal-degeneration-in-tauopathies-disease-relevance-and-underlying-mechanisms
#14
REVIEW
Andrew Kneynsberg, Benjamin Combs, Kyle Christensen, Gerardo Morfini, Nicholas M Kanaan
Tauopathies are a diverse group of diseases featuring progressive dying-back neurodegeneration of specific neuronal populations in association with accumulation of abnormal forms of the microtubule-associated protein tau. It is well-established that the clinical symptoms characteristic of tauopathies correlate with deficits in synaptic function and neuritic connectivity early in the course of disease, but mechanisms underlying these critical pathogenic events are not fully understood. Biochemical in vitro evidence fueled the widespread notion that microtubule stabilization represents tau's primary biological role and that the marked atrophy of neurites observed in tauopathies results from loss of microtubule stability...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29082468/tau-diagnostics-and-clinical-studies
#15
EDITORIAL
Illana Gozes, Günter Höglinger, James P Quinn, Nigel M Hooper, Kina Höglund
This short editorial provides our point of view of the first EURO TAU meeting focusing on tau diagnostics and clinical studies. We cover postmortem analyses toward the identification of new biomarkers, tau imaging as a diagnostic biomarker, cerebrospinal fluid (CSF) sampling with emphasis on tau fragments, blood tests and genetic evaluations for sporadic cases, treatment aspects, drug development and points for future developments toward disease modification of devastating tauopathies.
October 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29080085/dual-mtorc1-mtorc2-blocker-as-a-possible-therapy-for-tauopathy-in-cellular-model
#16
Mohamed Salama, Mahmoud Elhussiny, Alshimaa Magdy, Ahmed G Omran, Aziza Alsayed, Ramy Ashry, Wael Mohamed
Tauopathy comprises a group of disorders caused by abnormal aggregates of tau protein. In these disorders phosphorylated tau protein tends to accumulate inside neuronal cells (soma) instead of the normal axonal distribution of tau. A suggested therapeutic strategy for tauopathy is to induce autophagy to increase the ability to get rid of the unwanted tau aggregates. One of the key controllers of autophagy is mTOR. Blocking mTOR leads to stimulation of autophagy. Recently, unravelling molecular structure of mTOR showed that it is formed of two subunits: mTORC1/C2...
October 27, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29077582/neuroimaging-in-the-diagnosis-of-chronic-traumatic-encephalopathy-a-systematic-review
#17
Philip Sparks, Tim Lawrence, Stephan Hinze
OBJECTIVE: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repeated subconcussive and concussive head injury. Clinical features include cognitive, behavioral, mood, and motor impairments. Definitive diagnosis is only possible at postmortem. Here, the utility of neuroimaging in the diagnosis of CTE is evaluated by systematically reviewing recent evidence for changes in neuroimaging biomarkers in suspected cases of CTE compared with controls. DATA SOURCES: Providing an update on a previous systematic review of articles published until December 2014, we searched for articles published between December 2014 and July 2016...
October 25, 2017: Clinical Journal of Sport Medicine: Official Journal of the Canadian Academy of Sport Medicine
https://www.readbyqxmd.com/read/29077261/tau-directs-intracellular-trafficking-by-regulating-the-forces-exerted-by-kinesin-and-dynein-teams
#18
Abdullah R Chaudhary, Florian Berger, Christopher L Berger, Adam G Hendricks
Organelles, proteins, and mRNA are transported bidirectionally along microtubules by plus-end directed kinesin and minus-end directed dynein motors. Microtubules are decorated by microtubule-associated proteins (MAPs) that organize the cytoskeleton, regulate microtubule dynamics and modulate the interaction between motor proteins and microtubules to direct intracellular transport. Tau is a neuronal MAP that stabilizes axonal microtubules and crosslinks them into bundles. Dysregulation of tau leads to a range of neurodegenerative diseases known as tauopathies including Alzheimer's disease (AD)...
October 27, 2017: Traffic
https://www.readbyqxmd.com/read/29073081/trem2-deficiency-attenuates-neuroinflammation-and-protects-against-neurodegeneration-in-a-mouse-model-of-tauopathy
#19
Cheryl E G Leyns, Jason D Ulrich, Mary B Finn, Floy R Stewart, Lauren J Koscal, Javier Remolina Serrano, Grace O Robinson, Elise Anderson, Marco Colonna, David M Holtzman
Variants in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) were recently found to increase the risk for developing Alzheimer's disease (AD). In the brain, TREM2 is predominately expressed on microglia, and its association with AD adds to increasing evidence implicating a role for the innate immune system in AD initiation and progression. Thus far, studies have found TREM2 is protective in the response to amyloid pathology while variants leading to a loss of TREM2 function impair microglial signaling and are deleterious...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29067314/sar110894-a-potent-histamine-h3-receptor-antagonist-displays-disease-modifying-activity-in-a-transgenic-mouse-model-of-tauopathy
#20
Philippe Delay-Goyet, Véronique Blanchard, Nathalie Schussler, Mati Lopez-Grancha, Jean Ménager, Véronique Mary, Eric Sultan, Armelle Buzy, Jean-Claude Guillemot, Jeanne Stemmelin, Philippe Bertrand, Thomas Rooney, Laurent Pradier, Pascal Barnéoud
INTRODUCTION: Tau hyperphosphorylation and neurofibrillary tangles are histopathologic hallmarks of tauopathies. Histamine H3-receptor antagonists have been proposed to reduce tau hyperphosphorylation in preclinical models. METHODS: We evaluated the ability of SAR110894, a selective histamine H3-receptor antagonist, to inhibit tau pathology and prevent cognitive deficits in a tau transgenic mouse model (THY-Tau22). RESULTS: SAR110894 treatment for 6 months (but not 2 weeks) in THY-Tau22 mice decreased both tau hyperphosphorylation at pSer396-pSer404 (AD2 signal) in the hippocampus and the number of AT8 (pSer199/202-Thr205) positive cells in the cortex and decreased the formation of neurofibrillary tangles in the cortex, hippocampus, and amygdala...
November 2016: Alzheimer's & Dementia: Translational Research & Clinical Interventions
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