Добірка наукової літератури з теми "Phosphorylated tau"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся зі списками актуальних статей, книг, дисертацій, тез та інших наукових джерел на тему "Phosphorylated tau".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Статті в журналах з теми "Phosphorylated tau"
1
LITERSKY, Joel M., Gail V. W. JOHNSON, Ross JAKES, Michel GOEDERT, Michael LEE, and Peter SEUBERT. "Tau protein is phosphorylated by cyclic AMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II within its microtubule-binding domains at Ser-262 and Ser-356." Biochemical Journal 316, no. 2 (June 1, 1996): 655–60. http://dx.doi.org/10.1042/bj3160655.
Повний текст джерелаАнотація:
Phosphorylation of tau protein at Ser-262 has been shown to diminish its ability to bind to taxol-stabilized microtubules. The paired helical filaments (PHFs) found in Alzheimer's disease brain are composed of PHF-tau, which is hyperphosphorylated at multiple sites including Ser-262. However, protein kinase(s) able to phosphorylate this site are still under investigation. In this study, the ability of cyclic AMP-dependent protein kinase (cAMP-PK) and calcium/calmodulin-dependent protein kinase II (CaMKII) to phosphorylate tau at Ser-262, as well as Ser-356, is demonstrated by use of a monoclonal antibody (12E8) which has been shown to recognize tau when these sites are phosphorylated. Cleavage of cAMP-PK-phosphorylated tau at cysteine residues by 2-nitro-5-thiocyanobenzoic acid, which cuts the protein into essentially two fragments and separates Ser-262 from Ser-356, revealed that cAMP-PK phosphorylates both Ser-262 and Ser-356. In addition, phosphorylation with cAMP-PK or CaMKII of recombinant tau in which Ser-262, Ser-356 or both had been mutated to alanines, clearly demonstrated that cAMP-PK and CaMKII were able to phosphorylate both sites. Mitogen-activated protein kinase or protein kinase C did not phosphorylate tau at Ser-262 and/or Ser-356. Finally, evidence is presented that phosphorylation of both these sites occurs in cultured nerve cells under certain conditions, indicating their potential physiological relevance.
2
Sen, Tanusree, Pampa Saha, Tong Jiang та Nilkantha Sen. "Sulfhydration of AKT triggers Tau-phosphorylation by activating glycogen synthase kinase 3β in Alzheimer’s disease". Proceedings of the National Academy of Sciences 117, № 8 (12 лютого 2020): 4418–27. http://dx.doi.org/10.1073/pnas.1916895117.
Повний текст джерелаАнотація:
In Alzheimer’s disease (AD), human Tau is phosphorylated at S199 (hTau-S199-P) by the protein kinase glycogen synthase kinase 3β (GSK3β). HTau-S199-P mislocalizes to dendritic spines, which induces synaptic dysfunction at the early stage of AD. The AKT kinase, once phosphorylated, inhibits GSK3β by phosphorylating it at S9. In AD patients, the abundance of phosphorylated AKT with active GSK3β implies that phosphorylated AKT was unable to inactivate GSK3β. However, the underlying mechanism of the inability of phosphorylated AKT to phosphorylate GSK3β remains unknown. Here, we show that total AKT and phosphorylated AKT was sulfhydrated at C77 due to the induction of intracellular hydrogen sulfide (H2S). The increase in intracellular H2S levels resulted from the induction of the proinflammatory cytokine, IL-1β, which is a pathological hallmark of AD. Sulfhydrated AKT does not interact with GSK3β, and therefore does not phosphorylate GSK3β. Thus, active GSK3β phosphorylates Tau aberrantly. In a transgenic knockin mouse (AKT-KI+/+) that lacked sulfhydrated AKT, the interaction between AKT or phospho-AKT with GSK3β was restored, and GSK3β became phosphorylated. In AKT-KI+/+ mice, expressing the pathogenic human Tau mutant (hTau-P301L), the hTau S199 phosphorylation was ameliorated as GSK3β phosphorylation was regained. This event leads to a decrease in dendritic spine loss by reducing dendritic localization of hTau-S199-P, which improves cognitive dysfunctions. Sulfhydration of AKT was detected in the postmortem brains from AD patients; thus, it represents a posttranslational modification of AKT, which primarily contributes to synaptic dysfunction in AD.
3
Goedert, Michel. "Pinning down phosphorylated tau." Nature 399, no. 6738 (June 1999): 739–40. http://dx.doi.org/10.1038/21550.
Повний текст джерела
4
陈, 亦刚. "Abnormally Phosphorylated Tau and Tauopathies." International Journal of Psychiatry and Neurology 06, no. 02 (2017): 7–12. http://dx.doi.org/10.12677/ijpn.2017.62002.
Повний текст джерела
5
WOODS, Yvonne L., Philip COHEN, Walter BECKER, Ross JAKES, Michel GOEDERT, Xuemin WANG та Christopher G. PROUD. "The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bɛ at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase". Biochemical Journal 355, № 3 (24 квітня 2001): 609–15. http://dx.doi.org/10.1042/bj3550609.
Повний текст джерелаАнотація:
The substrate specificity of glycogen synthase kinase 3 (GSK3) is unusual in that efficient phosphorylation only occurs if another phosphoserine or phosphothreonine residue is already present four residues C-terminal to the site of GSK3 phosphorylation. One such substrate is the ε-subunit of rat eukaryotic protein-synthesis initiation factor 2B (eIF2Bε), which is inhibited by the GSK3-catalysed phosphorylation of Ser535. There is evidence that GSK3 is only able to phosphorylate eIF2Bε at Ser535 if Ser539 is already phosphorylated by another protein kinase. However, no protein kinases capable of phosphorylating Ser539 have so far been identified. Here we show that Ser539 of eIF2Bε, which is followed by proline, is phosphorylated specifically by two isoforms of dual-specificity tyrosine phosphorylated and regulated kinase (DYRK2 and DYRK1A), but only weakly or not at all by other ‘proline-directed’ protein kinases tested. We also establish that phosphorylation of Ser539 permits GSK3 to phosphorylate Ser535in vitro and that eIF2Bε is highly phosphorylated at Ser539in vivo. The DYRK isoforms also phosphorylate human microtubule-associated protein tau at Thr212in vitro, a residue that is phosphorylated in foetal tau and hyperphosphorylated in filamentous tau from Alzheimer's-disease brain. Phosphorylation of Thr212 primes tau for phosphorylation by GSK3 at Ser208in vitro, suggesting a more general role for DYRK isoforms in priming phosphorylation of GSK3 substrates.
6
Anderton, Brian H., Joanna Betts, Walter P. Blackstock, Jean-Pierre Brion, Sara Chapman, James Connell, Rejith Dayanandan, et al. "Sites of phosphorylation in tau and factors affecting their regulation." Biochemical Society Symposia 67 (February 1, 2001): 73–80. http://dx.doi.org/10.1042/bss0670073.
Повний текст джерелаАнотація:
The microtubule-associated protein, tau, is the principal component of paired helical filaments (PHFs) in Alzheimer's disease. PHF-tau is highly phosphorylated and a total of 25 sites of phosphorylation have so far been identified. Many of these sites are serine or threonine residues that are immediately followed in the sequence by proline residues, and hence are candidate phosphorylation sites for proline-directed kinases. In vitro, glycogen synthase kinase-3 (GSK-3), extracellular signal-related kinase-1 and -2, and mitogen-activated protein kinases, p38 kinase and c-jun N-terminal kinase, all phosphorylate many of these sites, although with different efficiencies for particular sites. Phosphorylation studies in transfected cells and neurons show that GSK-3 phosphorylates tau more extensively than do these other proline-directed kinases. Mutations in tau have been shown to affect in vitro phosphorylation of tau by GSK-3. The Arg406-->Trp (R406W) tau mutation also affects tau phosphorylation in cells.
7
Arai, Tetsuaki, Jian-Ping Guo, and Patrick L. McGeer. "Proteolysis of Non-phosphorylated and Phosphorylated Tau by Thrombin." Journal of Biological Chemistry 280, no. 7 (November 12, 2004): 5145–53. http://dx.doi.org/10.1074/jbc.m409234200.
Повний текст джерела
8
Goedert, M., R. Jakes, R. A. Crowther, P. Cohen, E. Vanmechelen, M. Vandermeeren, and P. Cras. "Epitope mapping of monoclonal antibodies to the paired helical filaments of Alzheimer's disease: identification of phosphorylation sites in tau protein." Biochemical Journal 301, no. 3 (August 1, 1994): 871–77. http://dx.doi.org/10.1042/bj3010871.
Повний текст джерелаАнотація:
Tau is a neuronal phosphoprotein the expression of which is developmentally regulated. A single tau isoform is expressed in fetal human brain but six isoforms are expressed in adult human brain, with the fetal isoform corresponding to the shortest adult isoform. Phosphorylation is also developmentally regulated, as fetal tau is phosphorylated at more sites than adult tau. In Alzheimer's disease, the six adult tau isoforms become hyperphosphorylated and form the paired helical filament (PHF), the major fibrous component of the neurofibrillary lesions. One way to identify phosphorylated sites in tau is to use antibodies that recognize phosphorylated residues within a specific amino acid sequence. We here characterize the two novel phosphorylation-dependent anti-tau antibodies AT270 and AT180 and identify their epitopes as containing phosphorylated Thr-181 and Thr-231 respectively. With these antibodies we show that these two threonine residues are partially phosphorylated in fetal and adult tau and almost fully phosphorylated in PHF tau. This result contrasts with previous studies of Ser-202 and Ser-396 which are partially phosphorylated in fetal tau, unphosphorylated in adult tau but almost fully phosphorylated in PHF tau.
9
Drummond, Eleanor, Geoffrey Pires, Claire MacMurray, Manor Askenazi, Shruti Nayak, Marie Bourdon, Jiri Safar, Beatrix Ueberheide, and Thomas Wisniewski. "Phosphorylated tau interactome in the human Alzheimer’s disease brain." Brain 143, no. 9 (August 19, 2020): 2803–17. http://dx.doi.org/10.1093/brain/awaa223.
Повний текст джерелаАнотація:
Abstract Accumulation of phosphorylated tau is a key pathological feature of Alzheimer’s disease. Phosphorylated tau accumulation causes synaptic impairment, neuronal dysfunction and formation of neurofibrillary tangles. The pathological actions of phosphorylated tau are mediated by surrounding neuronal proteins; however, a comprehensive understanding of the proteins that phosphorylated tau interacts with in Alzheimer’s disease is surprisingly limited. Therefore, the aim of this study was to determine the phosphorylated tau interactome. To this end, we used two complementary proteomics approaches: (i) quantitative proteomics was performed on neurofibrillary tangles microdissected from patients with advanced Alzheimer’s disease; and (ii) affinity purification-mass spectrometry was used to identify which of these proteins specifically bound to phosphorylated tau. We identified 542 proteins in neurofibrillary tangles. This included the abundant detection of many proteins known to be present in neurofibrillary tangles such as tau, ubiquitin, neurofilament proteins and apolipoprotein E. Affinity purification-mass spectrometry confirmed that 75 proteins present in neurofibrillary tangles interacted with PHF1-immunoreactive phosphorylated tau. Twenty-nine of these proteins have been previously associated with phosphorylated tau, therefore validating our proteomic approach. More importantly, 34 proteins had previously been associated with total tau, but not yet linked directly to phosphorylated tau (e.g. synaptic protein VAMP2, vacuolar-ATPase subunit ATP6V0D1); therefore, we provide new evidence that they directly interact with phosphorylated tau in Alzheimer’s disease. In addition, we also identified 12 novel proteins, not previously known to be physiologically or pathologically associated with tau (e.g. RNA binding protein HNRNPA1). Network analysis showed that the phosphorylated tau interactome was enriched in proteins involved in the protein ubiquitination pathway and phagosome maturation. Importantly, we were able to pinpoint specific proteins that phosphorylated tau interacts with in these pathways for the first time, therefore providing novel potential pathogenic mechanisms that can be explored in future studies. Combined, our results reveal new potential drug targets for the treatment of tauopathies and provide insight into how phosphorylated tau mediates its toxicity in Alzheimer’s disease.
10
Tseng, H. C., Q. Lu, E. Henderson, and D. J. Graves. "Phosphorylated tau can promote tubulin assembly." Proceedings of the National Academy of Sciences 96, no. 17 (August 17, 1999): 9503–8. http://dx.doi.org/10.1073/pnas.96.17.9503.
Повний текст джерелаДисертації з теми "Phosphorylated tau"
1
Kamble, Praful Narayan. "Role of TLR3/TLR4 and NF-kB in BAG2 mediated phosphorylated Tau degradation." reponame:Repositório Institucional da UFABC, 2015.
Знайти повний текст джерелаАнотація:
Orientador: Prof. Dr. Daniel Carneiro CarrettieroTese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Neurociência e Cognição, 2015.
Doenca de Alzheimer (DA) e uma doenca neurodegenerativa progressiva provocada por perda de sinapses e neuronios, caracterizado por disfuncao da memoria e comprometimento cognitivo global. O anormalmente hiperfosforilada, insoluvel, a proteina tau filamentosa mostrou-se ser o componente principal de emaranhados neurofibrilares, uma caracteristica patologica da DA. Neuroinflamacao e o indutor secundario resposta patologica a deposicao de A e morte celular neuronal associada com DA. Pesquisas documentaram o envolvimento de receptores Toll-like (TLRs) na neuroinflamacao, contribuindo para a patogenese da DA. Todos os TLR ativam as vias inflamatorias conservadas, ativando adicionalmente o Fator Nuclear-kB (NF-kB), resultando na libertacao e a producao de citocinas pro-inflamatorias. Entre a familia TLR, varios estudos indicaram o envolvimento de TLR3 e TLR4 contribuindo para neuroinflamacao. Alem disso, um corpo de dados indica o envolvimento de BAG2 na degradacao da tau fosforilada. Neste contexto, foi investigado o papel de TLR3 e TLR4 na modulacao da BAG2 promovida a degradacao de p-Tau em celulas SH-SY5Y. Neste estudo utilizamos LPS e pIpC para ativar TLR4 e TLR3 respectivamente. Linha de celulas SH-SY5Y foi usadae estabelecendo que o Tau induza a formacao de microtubulos sem limites que esta de acordo com a sua funcao como uma proteina associada amicro tubulos em DA. E tambem, utilizaram-se as celulas SH-SY5Y indiferenciadas uma vez que a expressao de BAG2 e inferior e indiferenciada, em comparacao com celulas diferenciadas. Neste estudo, a ativacao de TLR3 com diferentes concentracoes dem pIpC (1, 10, 50 e 100¿Êg/ml) resultou na regulacao negativa significativa de p-Tau em BAG2 expressao excessiva. Por outro lado, a ativacao de TLR4 com diferentes concentracoes de LPS (10, 50 e 100¿Êg/ml) resultaram em diminuicao dependente da dose na BAG2 expressao excessiva. Alem disso, usou-se JSH-23 para a inibicao de NF-kB. JSH-23 a uma concentracao de 25¿ÊM mostraram regulacao negativa significativa em p-Tau independente do BAG2 expressao excessiva e/ou a estimulacao de TLR3 e TLR4. Inibicao de NF-kB com JSH-23 25¿ÊM resultou na supra regulacao de transcricao significativa BAG2 endogena resultando na degradacao de ptau. Em contraste, a inibicao do NF-kB resultou na supra regulacao de HMW p-tau. BAG2 exogeno sobre a estimulacao TLR4 resultou nodecrescimo da regulacao de HMW p-tau. No entanto JSH-23 endogena induzida BAG2 falhou para regular negativamente HMW p-tau. A ativacao de TLR3/TLR4 nao mostrou toxicidade celular, nem a fosforilacao tau nas celulas SHSY5Y. Alem disso, a estimulacao por LPS na presenca/ausencia de sobre expressao BAG2 nao participa na proliferacao celular. No geral, os resultados demonstram a modulacao BAG2 em TLR4 e TLR3 estimulacao e inibicao de NF-kB degradacao em p-Tau e ou HMW p-Tau em DA.
Alzheimer¿s disease (AD) is a neurodegenerative disorder caused by progressive loss of synapses and neurons, characterized by memory dysfunction and global cognitive impairment. The abnormally hyperphosphorylated, insoluble, filamentous tau protein was shown to be the main component of NFTs, a pathological hallmark of AD. Neuroinflammation is the pathological secondary inducer response to deposition of A and neuronal cell death associated with AD. Considerable research has documented the involvement of Toll-like receptors (TLRs) in neuroinflammation, contributing to the pathogenesis of AD. All TLRs activate conserved inflammatory pathways, further activating nuclear factor-kB (NF-kB) resulting in the release and production of pro-inflammatory cytokines. Among the TLRs family, several studies have indicated the involvement of TLR3 and TLR4 contributing to neuroinflammation. Furthermore, a body of data indicates the involvement of BAG2 in phosphorylated Tau degradation. In this context we investigated the role of TLR3 and TLR4 in modulation of BAG2 promoted p-Tau degradation in SH-SY5Y cells. In this study we used LPS and pIpC to activate TLR4 and TLR3 respectively. SH-SY5Y cell line was used since it is established that the Tau induces the formation of microtubule bundles which is in accord with its function as a microtubule-associated protein in AD. And also, we used undifferentiated SH-SY5Y cells since the expression of BAG2 is lower in undifferentiated as compared to differentiated cell. In this study, activation of TLR3 with different concentration of pIpC (1, 10, 50 and 100ìg/mL) resulted in significant downregulation of p-Tau on BAG2 overexpression. On the other hand, activation of TLR4 with different concentration of LPS (10, 50 and 100ìg/mL) resulted in dose dependent decrease on BAG2 overexpression. . Further we used JSH-23 for NF-kB inhibition. JSH-23 at a concentration of 25ìM showed significant downregulation in p-Tau independent of BAG2 overexpression and/or on TLR4 and TLR3 stimulation. NF-kB inhibition with JSH-23 25ìM resulted in significant upregulation of endogenous BAG2 transcript resulting in p-Tau degradation. In contrast, NF-kB inhibition resulted in upregulation of HMW p-Tau. Exogenous BAG2 on TLR4 stimulation resulted in downregulation of HMW p-Tau. However JSH-23 induced endogenous BAG2 failed to downregulate HMW p-Tau. Activation of TLR3/TLR4 neither showed cell toxicity nor Tau phosphorylation in SH-SY5Y cells. Further LPS stimulation in presence/absence of BAG2 overexpression does not participate in cell proliferation. Overall, our findings demonstrate BAG2 modulation on TLR4 and TLR3 stimulation, and NF-kB inhibition in p-Tau and/or HMW p-Tau degradation in AD.
2
Adhikari, Rajan Deep. "MRI T2 Signal Changes Indicate Tau Pathophysiology in a Murine Alzheimer's Disease Model." BYU ScholarsArchive, 2017. https://scholarsarchive.byu.edu/etd/6944.
Повний текст джерелаАнотація:
Pathogenesis, diagnosis and treatment, the essential domains in medical practice, seem helpless to address Alzheimer's disease (AD). With a huge mortality rate, it is looming and threatening the socioeconomic barrier. Despite many different studies, the pathogenesis of AD remains inconclusive. However, growing numbers of studies suggest oxidative stress to contribute to the initiation and progression of AD. We propose an iron hypothesis: iron mediated oxidative damage by reactive oxygen species (ROS), which induces protective roles of amyloid beta and hyper-phosphorylated tau (HP-tau) to sequester iron and limit the disease. We propose to study such mechanism using transgenic mice models for AD, inducing oxidative stress to elevate intracellular iron, and analyze its co-localization with proteins using Magnetic Resonance Imaging (MRI), 1H Nuclear Magnetic Resonance (NMR) spectroscopy and Western blot. We report three primary findings: 1) a significant loss in T2 signal over bilateral hippocampi of transgenic mice compared to the wild types (WT) by three months, corresponding to early disease and the ability of proteins to sequestration iron. Ability of rescue treatments to impede disease progression reflected as preserved T2 signal intensities over these areas throughout our study period of nine months. 2) Concentration of zinc and its dual role in the presence or absence of oxidative stress reflected as loss of 1H NMR T2 measurement showed that higher concentrations of zinc were neuro protective when there was an active oxidative stress inducing condition, but neurotoxic and promote oxidative damage in normal condition. And 3) Different strains of mice, according to their transgene, expressed various proteins associated with AD. However, these expressions were in accordance with our iron-hypothesis.
3
Albaret, Marie Alexandra. "Rôle potentiel du virus herpes simplex de type I dans la maladie d'Alzheimer." Thesis, Lyon 1, 2009. http://www.theses.fr/2009LYO10117.
Повний текст джерелаАнотація:
L'étiologie de la forme sporadique de la maladie d'Alzheimer (AD) reste largement inconnue. Toutefois, une adéquation entre des facteurs environnementaux et génétiques est fortement probable. C'est ainsi que de nombreux arguments suggèrent que le virus herpes simplex de type 1 (HSV1) en infectant et en se répliquant dans le système nerveux central, puisse être un co-facteur impliqué dans le déclenchement et le développement de l'AD. Pour éprouver cette hypothèse, nous avons développé un modèle cellulaire constitué de neurones de rat infectés par HSV1 pour analyser les modifications viro-induites de leur expression génique. Il a été mis en évidence dans les neurones infectés : i) une augmentation de la production du peptide amyloïde Aβ42 et de Tau phosphorylée, ainsi que leur agrégation dans un agrésome intracellulaire ; ii) des variations du niveau de transcription de nombreux gènes très similaires à celles observées chez des patients AD. Par ailleurs, l'étude des mécanismes moléculaires de l'apoptose viro-induite dans ce modèle original a permis de mettre en évidence une corrélation entre l'activation des caspases et la production d'Aβ42 et une corrélation entre le phénomène d'apoptose avortée (abortosis) et la formation d'agrésome. De l'ensemble des ces résultats, il apparait que ce modèle cellulaire est représentatif de certains aspects des stades précoces de l'AD et conforte l'hypothèse qu'HSV1 serait un co-facteur dans la maladie d'AlzheimerThe origin of the sporadic form of the Alzheimer's disease (AD) remains still widely unknown. However, an adequacy between environmental and genetic factors is highly probable. Numerous arguments suggest that the virus herpes simplex of type 1 (HSV1) by infecting and replicating in the central nervous system, could be a co-factor involved in the AD process. To evaluate this hypothesis, we set up a model made of rat neurons infected by HSV1 in order to analyse the virally-induced modifications of their gene expression. Using this model we have shown: i) an over-production of the amyloid peptide Aß42 and of phosphorylated form of Tau accompanied by their concentration within an intracellular aggresome; ii) variations of the transcription levels of numerous genes equivalent to that observed in AD patients. Furthermore, the study of the molecular mechanisms underlying the virally-induced apoptosis allowed to point out a correlation between caspase activation and Aß42 production as well as a correlation between abortosis and aggresome formation. All together these results demonstrate that this cellular model represents, at least in part, some aspects of the early stages of AD and bring evidences that HSV1 could be a co-factor in the AD process
4
Alves, Steven Ribeiro. "The relevence of insulin signalling in Alzheimer's disease." Master's thesis, Universidade de Aveiro, 2017. http://hdl.handle.net/10773/22020.
Повний текст джерелаАнотація:
Mestrado em Biologia Molecular e CelularAlzheimer’s disease (AD) is the most common type of dementia worldwide. It is molecularly characterized by deposition of extracellular senile plaques (SPs) composed by aggregated amyloid beta (Aβ) peptide, the formation of neurofibrillary tangles (NFTs) derived from hyperphosphorylation of the microtubule-associated protein Tau, synaptic dysfunction due to the deposits of SPs and NFTs and oxidative stress induced by impaired metabolic pathways. The insulin signalling pathway can play a major role in diverse AD related pathways, such as APP cleavage, Tau hyperphosphorylation, Apolipoprotein E (ApoE) influence in insulin signalling efficiency and the insulin degrading enzyme, which is also the major Aβ degrading enzyme. Growing evidence links AD with type 2 diabetes (T2D) due to impaired insulin signalling (IS) and brain insulin resistance. In a cohort based study in the Aveiro region, a correlation between diabetes and poor cognitive scores in the Mini Mental State Examination (MMSE) test were observed, with a p-value of 0.072. Additionally, carriers of the allele ApoE-ɛ2 appeared to be protective against diabetes, in the literature the same allele appears to be protective for AD. Posteriorly, the analysis of protein interactions, via the development of interactome networks, identified several proteins involved in both AD and the IS pathways. Also, by correlating these pathways with the synapse proteome, a very high overlap was observed (88% for AD, 79% for IS and 96% for AD and IS coincident proteins), enforcing the importance of both pathways in synaptic signalling and plasticity. From gene ontology studies, it was possible to assess the principal biological processes and molecular functions of the dataset of proteins. For AD, response to stimulus, cellular component organization, cell communication, signalling, protein binding, receptor binding and kinase binding were categories with elevated representation. Regarding coincident proteins between AD and IS pathways, an increase in all categories was observed, meaning that insulin plays a pivotal role in many AD events. Finally, the analysis of SH-SY5Y differentiated cells treated with 0, 1, 10 and 100 nM of insulin for 0, 10 and 60 minutes, showed a decrease on the intracellular total levels of protein Tau and an increase in the phosphorylation at serine 396. Regarding the amyloid precursor protein (APP), increases in intracellular levels were observed, when treated with insulin for 10 minutes, followed by a decrease for 60 minutes exposure. The phosphorylation of APP at threonine 668, has previously been related to increased production of Aβ, by promoting APP cleavage via the amyloidogenic pathway. In cells treated with insulin, a clear increase was detected at the 10-minute time point. At 60 minutes, the levels of phosphorylation were low probably due to low total APP levels.
A doença de Alzheimer (DA) é o tipo mais comum de demência no mundo. É caracterizada molecularmente pela deposição extracelular de placas senis (PS) compostas por agregados do péptido amiloide beta (Aβ), pela formação de emaranhados neurofibrilares (EN) derivados da hiperfosforilação da proteína Tau, pela disfunção sináptica devido aos depósitos de PS e EN e também pelo stress oxidativo induzido pelo enfraquecimento das vias metabólicas. A via de sinalização da insulina desempenha um papel principal em diversas vias da DA, tal como na clivagem da APP, hiperfosforilação da proteína Tau, eficiência da sinalização da insulina influenciada pela Apolipoproteína E (ApoE) e pela enzima envolvida na degradação de insulina que também é a enzima principal na degradação de Aβ. Crescente evidência relaciona a DA com a diabetes de tipo 2 (T2D) devido ao mau funcionamento da sinalização pela insulina e da resistência cerebral à mesma. Num estudo baseado num cohort da região de Aveiro, foi observada uma correlação entre a diabetes e um mau resultado no teste do ‘Mini Mental State Examination’. Adicionalmente, também foi observada uma correlação entre os portadores do alelo ApoE-ɛ2 e um estado protetor contra a T2D. Este alelo também foi observado na literatura como sendo protetor contra a DA. Posteriormente, uma análise de interações entre proteínas, identificou várias proteínas envolvidas tanto na DA como na sinalização da insulina. Correlacionando estes dados com o proteoma da sinapse, foi possível observar que existe uma grande representação das duas condições e também das proteínas coincidentes às duas (88% para a DA, 79% para a sinalização da insulina e 96% para as proteínas relacionadas com ambas), reforçando o papel de ambas as vias na sinalização e plasticidade sináptica. Do estudo de ontologia genética para a DA, foi possível identificar diversas vias importantes, tais como, resposta a um estímulo, organização de componentes celulares, comunicação celular, ligação proteica e ligação a uma cinase. Em relação à sinalização da insulina, as mesmas categorias apareciam com maior representação, significando que a insulina tem um papel importante em muitos eventos da DA. Por fim, o tratamento de SH-SY5Y diferenciadas com 0, 1, 10 e 100 nM de insulina por 0, 10 e 60 minutos mostraram uma diminuição nos níveis intracelulares da proteína Tau e um aumento na sua fosforilação na serina 396. Em relação à proteína percursora amiloide (APP), o tratamento de insulina levou a um aumento nos níveis intracelulares, quando exposta por 10 minutos seguido por uma diminuição aos 60 minutos. Quanto à fosforilação da treonina 668 da APP, foi previamente demonstrado que um aumento na fosforilação desse resíduo, promove a clivagem pela via amiloidogénica, levando à produção de Aβ. Nas células tratadas com insulina, um aumento claro da fosforilação desse resíduo da APP foi observado aos 10 minutos. Aos 60 minutos, os níveis da fosforilação eram baixos provavelmente devido aos baixos níveis de APP total.
5
McAteer, Kelly Marie. "The role of Substance P in chronic traumatic encephalopathy." Thesis, 2018. http://hdl.handle.net/2440/115184.
Повний текст джерелаАнотація:
Chronic traumatic encephalopathy (CTE) is believed to be a neurodegenerative disease associated with contact sports and exposure to repetitive mild traumatic brain injury (rmTBI). CTE has attracted significant attraction over the past few years due to the high incidence of sports-related head injuries and the emergence of dementia-like symptoms many years following active play. In addition, patients with suspected CTE display a very unique pattern of hyperphosphorylated tau deposition post-mortem, with accumulation located at the base of the cortical sulci. To date, the link between exposure to rmTBI and the development of both dementia-like symptoms and post-mortem pathology associated with CTE has not been ascertained, highlighting the need for the study of potential mechanisms driving these processes.
Substance P (SP) is a neuropeptide involved in the process of neurogenic inflammation, which has been shown previously to be involved in many processes within the brain following traumatic brain injury (TBI) including blood brain barrier disruption and development of oedema. Significantly increased levels of SP have also been frequently observed following TBI, as well as other studies showing that SP release can increase with the application of more frequent and intense stimuli, such as that observed in rmTBI. It could therefore be that SP may contribute to the long term behavioural and pathological changes observed in CTE. Therefore the overall aims of this thesis were to fully ascertain the role of SP release following rmTBI and to determine whether the changes observed following rmTBI can be attenuated with a therapeutic intervention.
Significant increases in SP concentrations were observed following both rmTBI and severe TBI in the cortical regions in the acute phases of injury, although this did not appear to have a pronounced effect on tau as analysed by Western Blot (WB). However when analysed using immunohistochemistry changes in tau deposition were observed at the same timepoints. To further analyse the role that SP may play in these injury processes, blockade of the TRPV₁ receptor, where SP is believed to be released from when mechanically stimulated, was performed prior to injury. Administration of a TRPV₁ antagonist both prior to and following injury prevented SP release in severely injured animals. However in rmTBI animals, SP release was only attenuated in those pre-treated with a TRPV₁ antagonist.
Therefore to further assess the effects of SP release following rmTBI, administration of an NK₁ antagonist, which is known to block the effects of SP release, was employed following injury. It was found that the antagonists may have had an effect on the acute release of SP following rmTBI, however this did not translate to changes in long term outcomes. Overall the effects on tau phosphorylation were believed to be negligible in this study and the SP/NK₁ system did not appear to be involved.
To summarise, it is believed that SP release is indeed affected following rmTBI. However, it does not appear to be involved in the phosphorylation of tau in the acute or chronic phases of injury. However, there is still much to be discovered about the role of the SP/NK1 system and its potential involvement following rmTBI and these studies provide the groundwork for future developments in this area.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2018
6
CHEN, YI-YIN, and 陳怡吟. "Astragaloside IV and nesfatin-1 encapsulated into duel-functional phosphatidylserine liposomes grafted with leptin and wheat germ agglutinin activate anti-apototic pathway to stimulate dopamine production and block expression of phosphorylated tau protein." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/7ncy3m.
Повний текст джерелаАнотація:
碩士國立中正大學
化學工程研究所
107
The heap up of α-synuclein (α-syn) and its interaction with tau protein i trigger the onset of PD. The purpose of this study was to develop target specific liposomes incorporated with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol (CHOL), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and phosphatidy-l-serine (PS). PS with negative charge has high affinity towards α-syn Liposomes were loaded with anti-oxidant drug, astragaloside IV (AS-IV) and the specific inhibitory gene, nestifin-1 (NF-1) followed by surface modification with wheat germ agglutinin (WGA) and leptin (Lep). This study established two in vitro models of 1-methyl-4-phenylpyridinium (MPP+) induced toxic human neuroblastoma SH-SY5Y cells to mimic PD neurodegeneration and human blood-brain barrier (BBB). Experimental results demonstrated that increasing mole percentage of DSPC and PS increased the particles size, stability, entrapment efficiency, and reduced releasing rate of AS-IV and NF-1. Optimal mathematical statistics was established to determine the optimal composition ratio for liposomes to carry out in vitro experiments. In this study, the electrostatic interaction between PS and NF-1 was observed by NMR spectrum. The Western blotting data analysis of the in vitro PD model found that it can effectively increase the specific treatment of α-syn and protein aggregation by the interaction between PS and drugs. PS played a dual role by targeting α-syn and inhibiting the conversion of a β sheet structure into an αhelix structure. In the course of WGA-Lep-AS-IV-NF-1-PS-liposomes treatment, the combined activity of target specific ability from liposomes with drug, and following antioxidant pathway to decrease the expression of α-syn and simultaneously inhibit the expression of phosphor-tau by AS-IV. Moreover, NF-1 was be taken to the pathogen of α-syn accumulation through the electrostatic interaction with PS, and following the gene pathway to reduce the expression of α-syn by specifically inhibiting PTEN-induced kinase 1 (PINK1), and simultaneously inhibit glycogen synthase kinase 3 beta (GSK3β) pathway is effective in reducing the amount of p-tau (S396) expression. The images of immunocytochemistry staining assay evidenced the ability of liposomes specifically target Lep receptor and α-syn and improved the therapeutic efficiency of drugs. The coexistence of α-syn and protein in PD disease was an important mark, in this study, using dual-target liposomes, the aid of PS, and the contribution of drugs between materials interaction each other to achieve more effective treatment of PD.
7
Bigley, Andrew N. "Investigations on the Mechanism of Allosteric Activtion of Rabbit Muscle Glycogen Phosphorylase b by AMP." Thesis, 2009. http://hdl.handle.net/1969.1/ETD-TAMU-2009-05-483.
Повний текст джерелаАнотація:
Much work has been carried out on glycogen phosphorylase over the last seventy years. Interest has persisted due not only to the usefulness of phosphorylase as a model system of allostery, but also due to the connection to the disease state in type II diabetes. The bulk of research consists of structural studies utilizing the wild-type enzyme from rabbit muscle. In this study we have employed linkage analysis in combination with structural perturbations via site-directed mutagenesis to test kinetic models of activation of phosphorylase b by AMP, and to examine the roles of the N-terminus, the acidic patch, ?-helix 1 and the 280?s loop in activation by AMP. Experiments have been carried out on purified glycogen phosphorylase b variants to determine the effects of perturbations in vitro. The kinetic models of activation by AMP are found to be a relatively accurate description of kinetic behavior of wild-type phosphorylase b, but are found to be technically incorrect with respect to the absolute requirements of two equivalents of AMP to be bound prior to catalysis. Phosphorylase b demonstrates activity in the absence of AMP, though only at high concentrations of phosphate, and a hybrid phosphorylase b with only a single functional AMP binding sight shows slight activation. The truncate ?2-17 shows weakened binding to AMP and phosphate in the apo enzyme, but maintains activation by AMP to an affinity similar to that of wild-type, indicating that the N-terminus is not required for activation by AMP, but has a role in establishing the affinity for both AMP and phosphate in the apo enzyme. Perturbations of the acidic patch indicate that interactions between the acidic patch and the N-terminus enhance the affinities in the apo enzyme, suggesting that the structures of the N-terminus at the acidic patch may represent an active form of the enzyme. ?-helix 1 is found to have a role in homotropic cooperativity in phosphorylase b, but not in heterotropic activation by AMP, while the 280?s loop is confirmed to have a role in the heterotropic coupling between AMP and phosphate. Based on the findings in this study an alternate structural model of activation by AMP involving ?-helix 8 is proposed.
8
Brandenburg, Sören. "Über die differentielle Regulation von Ionenkanälen in spezifischen Nanodomänen atrialer und ventrikulärer Kardiomyozyten." Doctoral thesis, 2017. http://hdl.handle.net/11858/00-1735-0000-0023-3E50-C.
Повний текст джерелаЧастини книг з теми "Phosphorylated tau"
1
Tanaka, T., H. Yamamori, K. Wada-Isoe, I. Tsujio, and M. Takeda. "Activated Protein Kinases and Phosphorylated Tau Protein in Alzheimer Disease." In Molecular Neurobiology of Alzheimer Disease and Related Disorders, 225–35. Basel: KARGER, 2004. http://dx.doi.org/10.1159/000078542.
Повний текст джерела
2
Hugon, J., P. Sindou, M. Lesort, P. Couratier, F. Esclaire, and C. Yardin. "Modifications of Phosphorylated Tau Immunoreactivity Linked to Excitotoxicity in Neuronal Cultures." In Alzheimer’s Disease: Lessons from Cell Biology, 172–79. Berlin, Heidelberg: Springer Berlin Heidelberg, 1995. http://dx.doi.org/10.1007/978-3-642-79423-0_14.
Повний текст джерела
3
Blennow, Kaj, and Henrik Zetterberg. "The Neurochemistry of Alzheimer’s Disease: One of the Most Common Causes of Reduced Capability in the Adult Population." In International Perspectives on Aging, 81–93. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-78063-0_7.
Повний текст джерелаАнотація:
AbstractAlzheimer’s disease (AD) is the most common form of dementia and is characterised by the triad of amyloid plaques, tau pathology and neurodegeneration. Except for a strong association with the susceptibility gene, specifically the apolipoprotein E (APOE) ε4 allele, the pathogenesis of the most common age-related sporadic form of AD is largely unknown. However, several genetic and environmental risk factors have been proposed. A potential problem is that most population-based studies on AD risk-profiling have not used biomarkers reflecting amyloid and tau pathology to classify patients and controls. Given the complex pathophysiology of late-onset AD and the difficulties in correctly diagnosing AD on purely clinical grounds, this introduces a risk of misclassification of both control subjects and clinically diagnosed AD cases. Importantly, in recent years, there has been a very successful development of blood biomarkers for AD pathophysiologies, including brain amyloidosis (amyloid β ratio), tau pathology (phosphorylated tau) and neurodegeneration (neurofilament light). Numerous studies have shown these biomarkers to correlate with amyloid and tau pathology load evaluated by PET and with MRI measures of neurodegeneration, and to predict future cognitive decline. The employment of blood biomarkers in epidemiological studies may foster an understanding of which and how specifically lifestyle risk factors are linked to AD, and repeated blood sampling in intervention trials may provide evidence as to whether controlling lifestyle factors may affect specific AD pathophysiologies.
4
Pires, Geoffrey, Beatrix Ueberheide, Thomas Wisniewski, and Eleanor Drummond. "Use of Affinity Purification–Mass Spectrometry to Identify Phosphorylated Tau Interactors in Alzheimer’s Disease." In Methods in Molecular Biology, 263–77. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2655-9_14.
Повний текст джерела
5
Brion, J. P., A. M. Couck, J. L. Conreur, and J. N. Octave. "A Phosphorylated Tau Species Is Transiently Present in Developing Cortical Neurons and Is Not Associated with Stable Microtubules." In Alzheimer’s Disease: Lessons from Cell Biology, 150–71. Berlin, Heidelberg: Springer Berlin Heidelberg, 1995. http://dx.doi.org/10.1007/978-3-642-79423-0_13.
Повний текст джерела
6
Hampel, H., S. Teipel, F. Faltraco, S. Brettschneider, A. Goernitz, K. Buerger, and H. J. Moeller. "Advances in the Development of Biomarkers for Alzheimer�s Disease - From CSF Total Tau and Amyloid-β(1-42) Proteins to Phosphorylated Tau and Amyloid-β-Antibodies." In Molecular Neurobiology of Alzheimer Disease and Related Disorders, 134–56. Basel: KARGER, 2004. http://dx.doi.org/10.1159/000078534.
Повний текст джерела
7
Kinoshita, Eiji, Emiko Kinoshita-Kikuta, and Tohru Koike. "Enrichment of Low-Molecular-Weight Phosphorylated Biomolecules Using Phos-Tag Tip." In Neuromethods, 75–84. New York, NY: Springer New York, 2019. http://dx.doi.org/10.1007/978-1-4939-9662-9_7.
Повний текст джерела
8
Kinoshita-Kikuta, Emiko, Eiji Kinoshita, and Tohru Koike. "Phos-Tag Fluorescent Gel Staining for the Quantitative Detection of His- and Asp-Phosphorylated Proteins." In Methods in Molecular Biology, 73–78. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1186-9_6.
Повний текст джерела
9
Komis, George, Tomáš Takáč, Slávka Bekešová, Pavol Vadovič, and Jozef Šamaj. "Affinity-Based SDS PAGE Identification of Phosphorylated Arabidopsis MAPKs and Substrates by Acrylamide Pendant Phos-Tag™." In Methods in Molecular Biology, 47–63. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0922-3_5.
Повний текст джерела
10
Calderón-Garcidueñas, Lilian, Partha S. Mukherjee, Katharina Waniek, Max Holzer, Chih-kai Chao, Charles Thompson, Rubén Ruiz-Ramos, et al. "Non-Phosphorylated Tau in Cerebrospinal Fluid is a Marker of Alzheimer’s Disease Continuum in Young Urbanites Exposed to Air Pollution." In Advances in Alzheimer’s Disease. IOS Press, 2021. http://dx.doi.org/10.3233/aiad210040.
Повний текст джерелаАнотація:
Long-term exposure to fine particulate matter (PM2.5) and ozone (O3) above USEPA standards is associated with Alzheimer’s disease (AD) risk. Metropolitan Mexico City (MMC) children exhibit subcortical pretangles in infancy and cortical tau pre-tangles, NFTs, and amyloid phases 1–2 by the 2nd decade. Given their AD continuum, we measured in 507 normal cerebrospinal fluid (CSF) samples (MMC 354, controls 153, 12.82 ± 6.73 y), a high affinity monoclonal non- phosphorylated tau antibody (non-P-Tau), as a potential biomarker of AD and axonal damage. In 81 samples, we also measured total tau (T-Tau), tau phosphorylated at threonine 181 (P-Tau), amyloid-β1–42, BDNF, and vitamin D. We documented by electron microscopy myelinated axonal size and the pathology associated with combustion-derived nanoparticles (CDNPs) in anterior cingulate cortex white matter in 6 young residents (16.25 ± 3.34 y). Non-P-Tau showed a strong increase with age significantly faster among MMC versus controls (p = 0.0055). Aβ1–42 and BDNF concentrations were lower in MMC children (p = 0.002 and 0.03, respectively). Anterior cingulate cortex showed a significant decrease (p = <0.0001) in the average axonal size and CDNPs were associated with organelle pathology. Significant age increases in non-P-Tau support tau changes early in a population with axonal pathology and evolving AD hallmarks in the first two decades of life. Non-P-Tau is an early biomarker of axonal damage and potentially valuable to monitor progressive longitudinal changes along with AD multianalyte classical CSF markers. Neuroprotection of young urbanites with PM2.5 and CDNPs exposures ought to be a public health priority to halt the development of AD in the first two decades of life.
Тези доповідей конференцій з теми "Phosphorylated tau"
1
Sturm, Deborah, Alejandra Alonso, Christopher Corbo, Isaac Osores, and Cynthia Murillo. "Quantitative analysis of the effect of phosphorylated tau on cellular microfilament networks." In SPIE Medical Imaging, edited by John B. Weaver and Robert C. Molthen. SPIE, 2013. http://dx.doi.org/10.1117/12.2007056.
Повний текст джерела
2
Mariano, Luciano, Larissa Salvador, Patrícia Peles, Clarisse Friedlaender, Viviane Carvalho, Etelvina dos Santos, Leonardo de Souza, and Paulo Caramelli. "AT(N) MODEL AND ITS ASSOCIATION WITH NEUROPSYCHOLOGICAL MARKERS." In XIII Meeting of Researchers on Alzheimer's Disease and Related Disorders. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1980-5764.rpda019.
Повний текст джерелаАнотація:
Background: The National Institute on Aging and Alzheimer’s Association (NIA-AA) proposed the AT(N) model to diagnose Alzheimer’s disease (AD) considering some biomarkers: amyloid beta (A), phosphorylated tau (T), and neurodegeneration (N). Still, AT(N) correlation with cognitive markers is not yet covered. Objective: To investigate the neuropsychological profile of patients with CSF biomarkers according to AT(N) classification. Methods: Sixty-five patients with thorough neuropsychological data and results of CSF biomarkers were included in the study. We performed a cluster analysis using biomarkers results. The validity was checked by neuropsychological tests scores. Results: We found three clusters: Cluster 1 (n=24), classified as non-AD; Clusters 2 (n=9) and 3 (n=32), classified as AD. Cluster 2 had a higher burden of phosphorylated tau and total tau. All groups were similar regarding sociodemographics and functionality. AD groups had worse memory deficits than the non-AD cluster, but Cluster 2 was more affected than Cluster 3. No other cognitive difference was found, except in the Cubes subtest (Cluster 3>Cluster 2).Conclusion: Memory was the sole domain able to discriminate AD from non-AD, probably due to Cluster 1 heterogeneity. Further studies are warranted to explore this hypothesis. A smaller cluster with AD shows variability in the biomarker profile, which is relevant given its worse cognitive scores.
3
Chen, Dandan, Jin Li, Hongwei Liu, Lang Ao, and Qiushi Zhang. "Genome-Wide Association and Interaction Study on Quantitative Traits of CSF Phosphorylated Tau in ADNI cohort." In HP3C'22: 2022 6th International Conference on High Performance Compilation, Computing and Communications. New York, NY, USA: ACM, 2022. http://dx.doi.org/10.1145/3546000.3546008.
Повний текст джерела
4
Du, Xiaoxi, Yosef Koronyo, Chengshuai Yang, Maya Koronyo-Hamaoui та Liang Gao. "Label-Free Hyperspectral Imaging and Deep-Learning Prediction of Retinal Amyloid β-Protein and Phosphorylated Tau". У 2022 IEEE Photonics Conference (IPC). IEEE, 2022. http://dx.doi.org/10.1109/ipc53466.2022.9975636.
Повний текст джерела
5
Costa, Larissa Maria de Paula Rebouças da, Gabriel de Souza Torres, Kauan Alves Sousa Madruga, and Poliana Rafaela dos Santos. "Biomarkers in Alzheimer’s disease." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.670.
Повний текст джерелаАнотація:
Background: Alzheimer’s disease (AD) is the most common cause of dementia and cognitive dysfunction in old ages. AD is characterised by beta- amyloid (Aβ) plaques and neurofibrillary tangles of the hyper-phosphorylated Tau protein. It has an extensive preclinical stage, which emphasizes the importance of the biological components related to an early diagnostic: biomarkers. Objectives: After critical analysis of the selected literature, this review has the goal of describing the main biomarkers in AD and discussing different ways of detecting it. Methods: This review was elaborated after a literature review in the PubMed database, with 15 articles published between 2016 and 2021. The keywords were used with the boolean operator “AND”. Articles of meta-analysis, review and systematic review were selected. Results: It was found central biomarkers for the AD diagnostic, such as Tau and Aβ. The following tests were used: CSF puncture; blood tests; neuroimaging; saliva and mucosa samples. Aβ and Tau can be collected by CSF or PET-TC. Conclusions: Biomarkers play an important role in early AD diagnostic, even with limitations in the tests. The CSF and PET-TC are expensive methods, only used in atypical cases of AD. Reliable blood tests remain in development. In conclusion, there’s the need for more studies about alternative diagnostic tests, that are non-invasive and have low cost. Those developments can be beneficial for health plans, helping early diagnosis of AD.