keyword
MENU ▼
Read by QxMD icon Read
search

Tau oligomers

keyword
https://www.readbyqxmd.com/read/29311706/mechanistic-insights-into-remodeled-tau-derived-phf6-peptide-fibrils-by-naphthoquinone-tryptophan-hybrids
#1
V Guru KrishnaKumar, Ashim Paul, Ehud Gazit, Daniel Segal
Intra-cellular tau protein tangles and extra-cellular β-amyloid plaques are hallmarks of Alzheimer's disease (AD), characterized by the conversion of natively unfolded monomeric protein/peptide into misfolded β-sheet rich aggregates. Therefore, inhibiting the aggregation cascade or disassembling the pre-formed aggregates becomes a pivotal event in disease treatment. In the present study, we show that Naphthoquinone-Tryptophan hybrids, i.e., NQTrp and Cl-NQTrp significantly disrupted the pre-formed fibrillar aggregates of Tau-derived PHF6 (VQIVYK) peptide and full-length tau protein in vitro, in a dose-dependent manner as evident from ThS assay, CD spectroscopy, and TEM...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29300447/hsp70-inhibits-the-nucleation-and-elongation-of-tau-and-sequesters-tau-aggregates-with-high-affinity
#2
Franziska Kundel, Suman De, Patrick Flagmeier, Mathew H Horrocks, Magnus Kjaergaard, Sarah L Shammas, Sophie E Jackson, Christopher M Dobson, David Klenerman
As a key player of the protein quality control network of the cell, the molecular chaperone Hsp70 inhibits the aggregation of the amyloid protein tau. To date, the mechanism of this inhibition and the tau species targeted by Hsp70 remain unknown. This is partly due to the inherent difficulty of studying amyloid aggregates because of their heterogeneous and transient nature. Here, we used ensemble and single-molecule fluorescence measurements to dissect how Hsp70 counteracts the self-assembly process of K18 tau with the pathological deletion ∆K280...
January 4, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29276758/role-of-tau-acetylation-in-alzheimer-s-disease-and-chronic-traumatic-encephalopathy-the-way-forward-for-successful-treatment
#3
Brandon Lucke-Wold, Kay Seidel, Rub Udo, Bennet Omalu, Mark Ornstein, Richard Nolan, Charles Rosen, Joel Ross
Progressive neurodegenerative diseases plague millions of individuals both in the United States and across the world. The current pathology of progressive neurodegenerative tauopathies, such as Alzheimer's disease (AD), Pick's disease, frontotemporal dementia (FTD), and progressive supranuclear palsy, primarily revolves around phosphorylation and hyperphosphorylation of the tau protein. However, more recent evidence suggests acetylation of tau protein at lysine 280 may be a critical step in molecular pathology of these neurodegenerative diseases prior to the tau hyperphosphorylation...
2017: Journal of Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29273772/reducing-the-rna-binding-protein-tia1-protects-against-tau-mediated-neurodegeneration-in-vivo
#4
Daniel J Apicco, Peter E A Ash, Brandon Maziuk, Chelsey LeBlang, Maria Medalla, Ali Al Abdullatif, Antonio Ferragud, Emily Botelho, Heather I Ballance, Uma Dhawan, Samantha Boudeau, Anna Lourdes Cruz, Daniel Kashy, Aria Wong, Lisa R Goldberg, Neema Yazdani, Cheng Zhang, Choong Y Ung, Yorghos Tripodis, Nicholas M Kanaan, Tsuneya Ikezu, Pietro Cottone, John Leszyk, Hu Li, Jennifer Luebke, Camron D Bryant, Benjamin Wolozin
Emerging studies suggest a role for tau in regulating the biology of RNA binding proteins (RBPs). We now show that reducing the RBP T-cell intracellular antigen 1 (TIA1) in vivo protects against neurodegeneration and prolongs survival in transgenic P301S Tau mice. Biochemical fractionation shows co-enrichment and co-localization of tau oligomers and RBPs in transgenic P301S Tau mice. Reducing TIA1 decreased the number and size of granules co-localizing with stress granule markers. Decreasing TIA1 also inhibited the accumulation of tau oligomers at the expense of increasing neurofibrillary tangles...
January 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29246249/oligomeric-forms-of-amyloid-%C3%AE-protein-in-plasma-as-a-potential-blood-based-biomarker-for-alzheimer-s-disease
#5
Min Jeong Wang, SangHak Yi, Jee-Young Han, So Young Park, Jae-Won Jang, In Kook Chun, Sang Eun Kim, Byoung Sub Lee, Gwang Je Kim, Ji Sun Yu, Kuntaek Lim, Sung Min Kang, Young Ho Park, Young Chul Youn, Seong Soo A An, SangYun Kim
BACKGROUND: Soluble amyloid-β (Aβ) oligomers are the major toxic substances associated with the pathology of Alzheimer's disease (AD). The ability to measure Aβ oligomer levels in the blood would provide simple and minimally invasive tools for AD diagnostics. In the present study, the recently developed Multimer Detection System (MDS) for AD, a new enzyme-linked immunosorbent assay for measuring Aβ oligomers selectively, was used to detect Aβ oligomers in the plasma of patients with AD and healthy control individuals...
December 15, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29240990/wnt-signaling-loss-accelerates-the-appearance-of-neuropathological-hallmarks-of-alzheimer-s-disease-in-j20-app-transgenic-and-wild-type-mice
#6
Cheril Tapia-Rojas, Nibaldo C Inestrosa
Alzheimer's disease (AD) is a neurodegenerative pathology characterized by aggregates of amyloid-β (Aβ) and phosphorylated tau protein, synaptic dysfunction, and spatial memory impairment. The Wnt signaling pathway has several key functions in the adult brain and has been associated with AD, mainly as a neuroprotective factor against Aβ toxicity and tau phosphorylation. However, dysfunction of Wnt/β-catenin signaling might also play a role in the onset and development of the disease. J20 APPswInd transgenic (Tg) mouse model of AD was treated i...
December 14, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29239599/a-tau-derived-hexapeptide-acphf6-promotes-beta-amyloid-a%C3%AE-fibrillogenesis
#7
Tarek Mohamed, Sarbjeet Singh Gujral, Praveen P N Rao
We studied the interactions of a tau derived hexapeptide AcPHF6 with beta-amyloid peptides Aβ40 and Aβ42 which reveals its unusual ability to promote Aβ fibrillogenesis. The results demonstrate that the N-acetylated and C-amidated AcPHF6 hexapeptide can cause significant acceleration in Aβ40 and Aβ42 fibril growth. Aggregation kinetic studies at pH 7.4 show that at 25 μM, AcPHF6 hexapeptide was able to cause ~2.3-fold increase in Aβ40 fibrillogenesis dramatically changing the aggregation kinetics. In addition, AcPHF6 peptide was able to reduce cellular toxicity mediated by Aβ40 and Aβ42 in hippocampal neuronal cell line (HT22)...
December 14, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29234273/indirubin-derivative-7-bromoindirubin-3-oxime-7bio-attenuates-a%C3%AE-oligomer-induced-cognitive-impairments-in-mice
#8
Liping Chen, Chunhui Huang, Jieyi Shentu, Minjun Wang, Sicheng Yan, Fei Zhou, Zaijun Zhang, Chuang Wang, Yifan Han, Qinwen Wang, Wei Cui
Indirubins are natural occurring alkaloids extracted from indigo dye-containing plants. Indirubins could inhibit various kinases, and might be used to treat chronic myelocytic leukemia, cancer and neurodegenerative disorders. 7-bromoindirubin-3-oxime (7Bio), an indirubin derivative derived from indirubin-3-oxime, possesses inhibitory effects against cyclin-dependent kinase-5 (CDK5) and glycogen synthase kinase-3β (GSK3β), two pharmacological targets of Alzheimer's disease (AD). In this study, we have discovered that 2...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29191219/neurons-derived-from-sporadic-alzheimer-s-disease-ipscs-reveal-elevated-tau-hyperphosphorylation-increased-amyloid-levels-and-gsk3b-activation
#9
Anna Ochalek, Balázs Mihalik, Hasan X Avci, Abinaya Chandrasekaran, Annamária Téglási, István Bock, Maria Lo Giudice, Zsuzsanna Táncos, Kinga Molnár, Lajos László, Jørgen E Nielsen, Bjørn Holst, Kristine Freude, Poul Hyttel, Julianna Kobolák, András Dinnyés
BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia, affecting one in eight adults over 65 years of age. The majority of AD cases are sporadic, with unknown etiology, and only 5% of all patients with AD present the familial monogenic form of the disease. In the present study, our aim was to establish an in vitro cell model based on patient-specific human neurons to study the pathomechanism of sporadic AD. METHODS: We compared neurons derived from induced pluripotent stem cell (iPSC) lines of patients with early-onset familial Alzheimer's disease (fAD), all caused by mutations in the PSEN1 gene; patients with late-onset sporadic Alzheimer's disease (sAD); and three control individuals without dementia...
December 1, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29156571/studies-for-improving-a-rat-model-of-alzheimer-s-disease-icv-administration-of-well-characterized-%C3%AE-amyloid-1-42-oligomers-induce-dysfunction-in-spatial-memory
#10
Ágnes Kasza, Botond Penke, Zsuzsanna Frank, Zsolt Bozsó, Viktor Szegedi, Ákos Hunya, Klaudia Németh, Gábor Kozma, Lívia Fülöp
During the past 15 years, several genetically altered mouse models of human Alzheimer's disease (AD) have been developed. These costly models have greatly facilitated the evaluation of novel therapeutic approaches. Injecting synthetic β-amyloid (Aβ) 1-42 species into different parts of the brain of non-transgenic rodents frequently provided unreliable results, owing to a lack of a genuine characterization of the administered Aβ aggregates. Previously, we have published a new rat AD-model in which protofibrillar-fibrillar Aβ1-42 was administered into rat entorhinal cortex (Sipos 2007)...
November 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29137322/the-c-jun-n-terminal-kinase-plays-a-key-role-in-ocular-degenerative-changes-in-a-mouse-model-of-alzheimer-disease-suggesting-a-correlation-between-ocular-and-brain-pathologies
#11
Lucia Buccarello, Alessandra Sclip, Matteo Sacchi, Anna Maria Castaldo, Ilaria Bertani, Andrea ReCecconi, Silvia Maestroni, Gianpaolo Zerbini, Paolo Nucci, Tiziana Borsello
Recently a range of ocular manifestations such as retinal and lens amyloid-beta accumulation and retinal nerve fiber layer loss have been proposed as potential biomarkers in Alzheimer disease (AD). The TgCRND8 mouse model of AD exhibits age-dependent amyloid β (Aβ) oligomers accumulation and cognitive defects, amyloid plaques and hyperphosphorylated Tau deposition and inflammation. We proved the correlation between ocular pathologies and AD, observing increased levels of p-APP and p-Tau, accumulation of Aβ oligomers in the retina, eye, and optic nerve...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29118388/near-infrared-light-decreases-synaptic-vulnerability-to-amyloid-beta-oligomers
#12
Michele M Comerota, Balaji Krishnan, Giulio Taglialatela
Synaptic dysfunction due to the disrupting binding of amyloid beta (Aβ) and tau oligomers is one of the earliest impairments in Alzheimer's Disease (AD), driving initial cognitive deficits and clinical manifestation. Consequently, there is ample consensus that preventing early synaptic dysfunction would be an effective therapeutic strategy for AD. With this goal in mind, we investigated the effect of a treatment of mice with near infrared (NIR) light on synaptic vulnerability to Aβ oligomers. We found that Aβ oligomer binding to CNS synaptosomes isolated from wild type (wt) mice treated with NIR light was significantly reduced and the resulting suppression of long term potentiation (LTP) by Aβ oligomers was prevented...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29103036/the-unexpected-role-of-a%C3%AE-1-42-monomers-in-the-pathogenesis-of-alzheimer-s-disease
#13
Elena Tamagno, Michela Guglielmotto, Debora Monteleone, Giusi Manassero, Valeria Vasciaveo, Massimo Tabaton
Amyloid-β (Aβ) has been proposed as a biomarker and a drug target for the therapy of Alzheimer's disease (AD). The neurotoxic entity and relevance of each conformational form of Aβ to AD pathology is still under debate; Aβ oligomers are considered the major killer form of the peptide whereas monomers have been proposed to be involved in physiological process. Here we reviewed some different effects mediated by monomers and oligomers on mechanisms involved in AD pathogenesis such as autophagy and tau aggregation...
October 30, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29063514/biomarkers-of-neuronal-injury-and-amyloid-metabolism-in-the-cerebrospinal-fluid-of-patients-infected-with-hiv-1-subtypes-b-and-c
#14
Sérgio Monteiro de Almeida, Clea E Ribeiro, Indianara Rotta, Mauro Piovesan, Bin Tang, Florin Vaida, Sonia Mara Raboni, Scott Letendre, Michael Potter, Meire S Batistela Fernandes, Ronald J Ellis
Based on prior reports that the HIV-1 Tat protein modulates amyloid-beta (Aβ) metabolism, this study aimed to compare CSF neural injury biomarkers between 27 patients with HIV subtype B, 26 patients with HIV subtype C, 18 healthy HIV-negative controls, and 24 patients with Alzheimer's disease (AD). Immunoassays were used to measure soluble amyloid precursor protein α and β (sAPPα, sAPPβ), Aβ oligomers 38, 40, 42, and Aβ-total; phosphorylated tau (P-tau181), and total tau (T-tau). Comparisons between HIV(+) and HIV(-) (including AD) were adjusted by linear regression for gender and age; HIV subtype comparisons were adjusted for nadir CD4 and plasma viral load suppression...
October 23, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/29053786/tau-hyperphosphorylation-induces-oligomeric-insulin-accumulation-and-insulin-resistance-in-neurons
#15
Patricia Rodriguez-Rodriguez, Anna Sandebring-Matton, Paula Merino-Serrais, Cristina Parrado-Fernandez, Alberto Rabano, Bengt Winblad, Jesús Ávila, Isidre Ferrer, Angel Cedazo-Minguez
Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathological conditions. Here, we report that insulin is accumulated and retained as oligomers in hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of the most prevalent human tauopathies. The intraneuronal accumulation of insulin is directly dependent on tau hyperphosphorylation, and follows the tauopathy progression...
October 13, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29021554/human-tau-p301l-overexpression-results-in-tau-hyperphosphorylation-without-neurofibrillary-tangles-in-adult-zebrafish-brain
#16
Mehmet I Cosacak, Prabesh Bhattarai, Ledio Bocova, Tim Dzewas, Violeta Mashkaryan, Christos Papadimitriou, Kerstin Brandt, Heike Hollak, Christopher L Antos, Caghan Kizil
Microtubule-associated TAU protein is a pathological hallmark in Alzheimer's disease (AD), where hyperphosphorylation of TAU generates neurofibrillary tangles. To investigate the effects of TAU in a regenerative adult vertebrate brain system, we generated a cre/lox-based transgenic model of zebrafish that chronically expresses human TAU(P301L), which is a variant of human TAU protein that forms neurofibrillary tangles in mouse models and humans. Interestingly, we found that although chronic and abundant expression of TAU(P301L) starting from early embryonic development led to hyperphosphorylation, TAU(P301L) did not form oligomers and neurofibrillary tangles, and did not cause elevated apoptosis and microglial activation, which are classical symptoms of tauopathies in mammals...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28984591/curcumin-inhibits-tau-aggregation-and-disintegrates-preformed-tau-filaments-in-vitro
#17
Jitendra Subhash Rane, Prasenjit Bhaumik, Dulal Panda
The pathological aggregation of tau is a common feature of most of the neuronal disorders including frontotemporal dementia, Parkinson's disease, and Alzheimer's disease. The inhibition of tau aggregation is considered to be one of the important strategies for treating these neurodegenerative diseases. Curcumin, a natural polyphenolic molecule, has been reported to have neuroprotective ability. In this work, curcumin was found to bind to adult tau and fetal tau with a dissociation constant of 3.3±0.4 and 8±1 μM, respectively...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28982375/pkr-involvement-in-alzheimer-s-disease
#18
REVIEW
Jacques Hugon, François Mouton-Liger, Julien Dumurgier, Claire Paquet
BACKGROUND: Brain lesions in Alzheimer's disease (AD) are characterized by Aβ accumulation, neurofibrillary tangles, and synaptic and neuronal vanishing. According to the amyloid cascade hypothesis, Aβ1-42 oligomers could trigger a neurotoxic cascade with kinase activation that leads to tau phosphorylation and neurodegeneration. Detrimental pathways that are associated with kinase activation could also be linked to the triggering of direct neuronal death, the production of free radicals, and neuroinflammation...
October 5, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28962864/blocking-sirt1-inhibits-cell-proliferation-and-promotes-aging-through-the-pi3k-akt-pathway
#19
Hongyan Li, Rong Wang
AIMS: Alzheimer's disease (AD) is the most prevalent age-related disease and the most common cause of dementia in the elderly. Its hallmark neuropathological features are the presence of amyloid-beta oligomers and neurofibrillary tangles that are composed of hyperphosphorylated tau protein. SIRT1 has been shown to have a neuroprotective effect; however, its working mechanisms are not well understood. This study aimed to address this issue. MAIN METHODS: We used an in vitro neuronal SH-SY5Y cell culture model to investigate the effect of SIRT1 knockdown on cell survival, proliferation, functionality, and cytotoxicity...
December 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28927263/molecular-and-cellular-basis-of-neurodegeneration-in-alzheimer-s-disease
#20
REVIEW
Sangyun Jeong
The most common form of senile dementia is Alzheimer's disease (AD), which is characterized by the extracellular deposition of amyloid β-peptide (Aβ) plaques and the intracellular formation of neurofibrillary tangles (NFTs) in the cerebral cortex. Tau abnormalities are commonly observed in many neurodegenerative diseases including AD, Parkinson's disease, and Pick's disease. Interestingly, tau-mediated formation of NFTs in AD brains shows better correlation with cognitive impairment than Aβ plaque accumulation; pathological tau alone is sufficient to elicit frontotemporal dementia, but it does not cause AD...
September 30, 2017: Molecules and Cells
keyword
keyword
48349
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"