Rose Bengal inhibits ß-amyloid oligomers-induced tau hyperphosphorylation via acting on Akt and CDK5 kinases.

RATIONALE: Tau hyperphosphorylation and aggregation is considered as a main pathological mechanism underlying Alzheimer's disease (AD). Rose Bengal (RB) is a synthetic dye used for disease diagnosis, which was reported to inhibit tau toxicity via inhibiting tau aggregation in Drosophila. However, it was unknown if RB could produce anti-AD effects in rodents. OBJECTIVES: The research aimed to investigate if and how RB could prevent ß-amyloid (Aß) oligomers-induced tau hyperphosphorylation in rodents. METHODS AND RESULTS: RB was tested in vitro (0.3-1 µM) and prevented Aß oligomers-induced tau hyperphosphorylation in PC12 cells. Moreover, RB (10-30 mg/kg, i.p.) effectively attenuated cognitive impairments induced by Aß oligomers in mice. Western blotting analysis demonstrated that RB significantly increased the expression of pSer473-Akt, pSer9-glycogen synthase kinase-3ß (GSK3ß) and reduced the expression of cyclin-dependent kinase 5 (CDK5) both in vitro and in vivo. Molecular docking analysis suggested that RB might directly interact with GSK3ß and CDK5 by acting on ATP binding sites. Gene Ontology enrichment analysis indicated that RB might act on protein phosphorylation pathways to inhibit tau hyperphosphorylation. CONCLUSIONS: RB was shown to inhibit tau neurotoxicity at least partially via inhibiting the activity of GSK3ß and CDK5, which is a novel neuroprotective mechanism besides the inhibition of tau aggregation. As tau hyperphosphorylation is an important target for AD therapy, this study also provided support for investigating the drug repurposing of RB as an anti-AD drug candidate.

6-Methyl-pyridine-2(1H)-thione.

There are two unique mol-ecules in the asymmetric unit of the title pyridine-thione derivative, C(6)H(7)NS, each of which adopts the thione rather than the mercaptan form. The rings in both mol-ecules are essentially planar, with maximum deviations from the least-squares planes through all non-H atoms of 0.021 (2) and 0.017 (2) Å. In the crystal structure, the mol-ecules form centrosymmetric cyclic dimers through inter-molecular N-H⋯S hydrogen bonds. Additional C-H(meth-yl)⋯S inter-actions generate a three-dimensional network.

6-Methyl-2-pyridyl N-acetyl-1-thio-ß-d-glucosa-minide methanol monosolvate.

In the title compound, C(14)H(20)N(2)O(5)S·CH(4)O, the pyran-ose and pyridine rings are linked through an S atom. The pyran-ose ring has a normal chair conformation. An intra-molecular O-H⋯N hydrogen bond occurs. Inter-molecular O-H⋯O, N-H⋯O, O-H⋯N and weak C-H⋯O hydrogen bonding is present in the crystal structure.

3,3'-(2,2'-Bi-1H-imidazole-1,1'-diyl)dipropanol.

In the title compound, C(12)H(18)N(4)O(2), unlike other unconjugated disubstituted biimidazole derivatives reported so far, the two imidazole rings in a trans conformation exhibit a large planar rotation angle of 51.27 (4)°, and consist of half-mol-ecule asymmetric units related by a twofold rotation. The mol-ecules are linked into a three-dimensional framework with a parallel laminated construction via O-H⋯N and C-H⋯O inter-actions.

Di-tert-butyl 3,3'-(2,2'-bi-1H-imidazole-1,1'-di-yl)dipropanoate.

In the title compound, C(20)H(20)N(4)O(4), the complete molecule is generated by a crystallographic centre of symmetry. The conformation is stabilized by two intramolecular C-H⋯N links.

Bis(2,2'-biimidazole-κN,N')bis-(2-bromo-fumarato-κO)copper(II).

In the title compound, [Cu(C(4)H(2)BrO(4))(2)(C(6)H(6)N(4))(2)], the central Cu(II) atom lies on an inversion center and is six-coordinated in an octahedral geometry by four N atoms from two chelating biimidazole mol-ecules in the equatorial plane and two O atoms from two 2-bromo-fumarate ligands in the axial positions. O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds lead to a three-dimensional network.

[Lanthanide ion luminescence probe: low temperature phase transition of EuS4N complex].

Fluorescence spectrum of EuS4N complex at low temperature is very different from that at room temperature. When temperature changes, shapes of both excitation and emission spectra change dramatically at about 160 K, which is taken as an indicator of the structural change of EuS4N. Peak splitting of 5D0-->7F0 also indicates that there are two different types of coordination structure for Eu3+ ions at low temperature, while only one at room temperature. Thermal effect for the structure transition is also deduced from the relation between fluorescence intensity and temperature changing manner. These results were in good accordance with directly measurement on sample temperature. The reason for the structure change is also discussed from the structure of the EuS4N complex. This study proved that lanthanide luminescent probe, as a complementarity to X-ray diffraction technique, should be an effective tool in low temperature crystal structure study.