Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alzheimer's disease is defined in part by the intraneuronal accumulation of filaments comprised of the microtubule associated protein tau. Because animal model studies suggest that a toxic gain of function accompanies tau aggregation in neurons, selective pharmacological inhibitors of the process may have utility in slowing neurodegeneration. Here, the properties of a candidate small molecule inhibitor of tau fibrillization, 3-(2-hydroxyethyl)-2-[2-[[3-(2-hydroxyethyl)-5-methoxy-2-benzothiazolylidene]methyl]-1-butenyl]-5-methoxybenzothiazolium (N744), were characterized in vitro using transmission electron microscopy. N744 inhibited arachidonic acid-induced aggregation of full-length, four-repeat tau protein at substoichiometric concentrations relative to total tau and with an IC(50) of approximately 300 nM. Inhibition was accompanied by a dose-dependent decrease in the number concentration of filaments, suggesting that N744 interfered with tau filament nucleation. Stoichiometric concentrations of N744 also promoted tau disaggregation when added to mature synthetic filaments. Disaggregation followed first-order kinetics and was accompanied by a steady decrease in filament number, suggesting that N744 promoted endwise loss of tau molecules with limited filament breakage. N744 at substoichiometric concentrations did not inhibit Abeta and alpha-synuclein aggregation, indicating it was tau selective under these conditions. Because of its activity in vitro, N744 may offer a pharmacological approach to the role of tau fibrillization in neurodegeneration.
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PMID:Ligand-dependent inhibition and reversal of tau filament formation. 1500 23

In this study, a simple and highly selective homogeneous sandwich assay was developed for fast and ultrasensitive detection of the tau protein using a combination of monoclonal antitau functionalized hybrid magnetic nanoparticles and polyclonal antitau immobilized gold nanoparticles as the recognition and surface-enhanced Raman scattering (SERS) component, respectively. The magnetic silica particles were first coated with poly(2-hydroxyethyl methacrylate) via surface-mediated reversible addition-fragmentation chain transfer (RAFT) polymerization and then biofunctionalized with monoclonal antitau, which are both specific for tau and can be collected via a simple magnet. After separating tau from the sample matrix, they were sandwiched with the SERS substrate composed of polyclonal antitau and 5,5-dithiobis(2-dinitrobenzoic acid) on gold nanoparticles. The correlation between the tau concentration and SERS signal was found to be linear within the range of 25 fM to 500 nM. The limit of detection for the sandwich assay is less than 25 fM. Moreover, the sandwich assay was also evaluated for investigating the tau specificity on bovine serum albumin and immunoglobulin G.
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PMID:A SERS-based sandwich assay for ultrasensitive and selective detection of Alzheimer's tau protein. 2388 27