scholarly journals Correction to Macrocyclic β-Sheet Peptides That Inhibit the Aggregation of a Tau-Protein-Derived Hexapeptide

2012 ◽  
Vol 134 (42) ◽  
pp. 17832-17832 ◽  
Author(s):  
Jing Zheng ◽  
Cong Liu ◽  
Michael R. Sawaya ◽  
Balraju Vadla ◽  
Shafiullah Khan ◽  
...  
Keyword(s):  
Tau Protein ◽  
Β Sheet

scholarly journals Macrocyclic β-Sheet Peptides That Inhibit the Aggregation of a Tau-Protein-Derived Hexapeptide

2011 ◽  
Vol 133 (9) ◽  
pp. 3144-3157 ◽  
Author(s):  
Jing Zheng ◽  
Cong Liu ◽  
Michael R. Sawaya ◽  
Balraju Vadla ◽  
Shafiullah Khan ◽  
...  
Keyword(s):  
Tau Protein ◽  
Β Sheet

scholarly journals The Fumarprotocetraric Acid Inhibits Tau Covalently, Avoiding Cytotoxicity of Aggregates in Cells

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3760
Author(s):  
Camila González ◽  
Constanza Cartagena ◽  
Leonardo Caballero ◽  
Francisco Melo ◽  
Carlos Areche ◽  
...  
Keyword(s):  
Cell Culture ◽  
Tau Protein ◽  
Deleterious Effect ◽  
Membrane Damage ◽  
Mechanisms Of Action ◽  
Pathological Mechanism ◽  
Cysteine Labeling ◽  
Β Sheet ◽  
Covalent Interactions ◽  
Pathological Confirmation

Neurodegenerative disorders, including Tauopathies that involve tau protein, base their pathological mechanism on forming proteinaceous aggregates, which has a deleterious effect on cells triggering an inflammatory response. Moreover, tau inhibitors can exert their mechanism of action through noncovalent and covalent interactions. Thus, Michael’s addition appears as a feasible type of interaction involving an α, β unsaturated carbonyl moiety to avoid pathological confirmation and further cytotoxicity. Moreover, we isolated three compounds from Antarctic lichens Cladonia cariosa and Himantormia lugubris: protolichesterinic acid (1), fumarprotocetraric acid (2), and lichesterinic acid (3). The maleimide cysteine labeling assay showed that compounds 1, 2, and 3 inhibit at 50 µM, but compounds 2 and 3 are statistically significant. Based on its inhibition capacity, we decided to test compound 2 further. Thus, our results suggest that compound 2 remodel soluble oligomers and diminish β sheet content, as demonstrated through ThT experiments. Hence, we added externally treated oligomers with compound 2 to demonstrate that they are harmless in cell culture. First, the morphology of cells in the presence of aggregates does not suffer evident changes compared to the control. Additionally, the externally added aggregates do not provoke a substantial LDH release compared to the control, indicating that treated oligomers do not provoke membrane damage in cell culture compared with aggregates alone. Thus, in the present work, we demonstrated that Michael’s acceptors found in lichens could serve as a scaffold to explore different mechanisms of action to turn tau aggregates into harmless species.

scholarly journals Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer’s disease

2017 ◽  
Vol 32 (1) ◽  
pp. 945-953 ◽  
Author(s):  
Alberto Cornejo ◽  
Felipe Aguilar Sandoval ◽  
Leonardo Caballero ◽  
Luis Machuca ◽  
Patricio Muñoz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Rosmarinic Acid ◽  
Vibrational Modes ◽  
Β Sheet

scholarly journals Lipid membrane templated misfolding and self-assembly of intrinsically disordered tau protein

2020 ◽  
Author(s):  
Jaroslaw Majewski ◽  
Emmalee M. Jones ◽  
Crystal M. Vander Zanden ◽  
Jacek Biernat ◽  
Eckhard Mandelkow ◽  
...  
Keyword(s):  
Phase Separation ◽  
Tau Protein ◽  
Self Assembly ◽  
Electrostatic Interactions ◽  
Lipid Membrane ◽  
Tau Proteins ◽  
Lipid Monolayer ◽  
Intrinsically Disordered ◽  
Tau Aggregation ◽  
Β Sheet

AbstractThe aggregation of the intrinsically disordered tau protein into highly ordered β-sheet fibrils is implicated in many neurodegenerative disorders. Fibrillation mechanism remains unresolved, particularly early events that trigger tau misfolding and assembly. We investigated the role membrane plays in modulating aggregation of three tau variants, the largest isoform hTau40, the truncated construct K18, and a hyperphosphorylation mutant hTau40/3Epi. Despite being charged and soluble, tau proteins were also highly surface active and favorably interacted with anionic, but not zwitterionic, lipid monolayer at the air/water interface. Membrane binding induced macroscopic tau phase separation and β-sheet-rich tau oligomer formation. Concomitantly, membrane morphology and lipid packing became disrupted. Our findings support a general tau aggregation mechanism wherein tau’s inherent surface activity and favorable electrostatic interactions drive tau-membrane association, inducing tau phase separation that is accompanied by misfolding and self-assembly of disordered tau into β-sheet-rich oligomers, which subsequently seed fibrillation and deposition into diseased tissues.

Was unterscheidet die Subtypen der Creutzfeldt-Jakob-Krankheit von anderen Demenzen mit initialen psychiatrischen Auffälligkeiten?

2003 ◽  
Vol 01 (01) ◽  
pp. 24-29
Author(s):  
H. Wormstall ◽  
M. Bartels ◽  
G.W. Eschweiler
Keyword(s):  
Tau Protein ◽  
Fur Protein ◽  
T2 Mri ◽  
Codon 129

ZusammenfassungSeit dem Nachweis boviner spongiformer Enzephalopathie (BSE) unter Rindern in Deutschland im November 2000 ist die Gefahr, an der neuen Variante der Creutzfeld-Jakob-Krankheit (vCJD) zu erkranken, auch hierzulande größer geworden. Diese Übersicht schildert die Differenzialdiagnostik von Demenzerkrankungen mit initialen psychiatrischen Auffälligkeiten im jüngeren und höheren Alter. Besonderer Wert wird auf die Unterschiede zwischen der sporadischen Creutzfeld-Jakob-Krankheit (sCJD) und der vCJD gelegt. Neben den klinischen und initial meist psychiatrisch geprägten Verläufen werden neuere laborchemische, molekulargenetische und neuroradiologische Aspekte dieser beiden Prionkrankheiten dargestellt. Der Liquor ist in den meisten Fällen positiv für Protein 14-3-3, Tau-Protein und Neuron-spezifische Enolase (NSE). Nur bei bestimmten molekulargenetisch am Codon 129 des Prionproteins determinierten Subgruppen der sCJD-Patienten, nicht aber bei vCJD-Patienten, finden sich im EEG periodische scharfe Wellen. In der Frühdiagnostik der sCJD kann vor allem die diffusionsgewichtete MRI eingesetzt werden. Bei den jüngeren vCJD-Patienten findet man neben den psychiatrischen Symptomen Parästhesien, erst später eine Demenz und Ataxie von mehr als 6 Monaten Dauer sowie T2-MRI-Signalhyperintensitäten im Pulvinar. Als weitere Differenzialdiagnosen der verschiedenen CJD-Subtypen wird auch die wenig bekannte Hashimoto-Enzephalopathie näher beschrieben.

The role of tau-protein in the diagnosis of cognitive impairment in diabetes

2020 ◽  
Author(s):  
Mariia Matveeva ◽  
Julia Samoilova ◽  
Natalie Zhukova
Keyword(s):  
Cognitive Impairment ◽  
Tau Protein
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