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A number of epidemiological studies have established a link between Alzheimer's disease (AD) and diabetes mellitus (DM). So, nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in the treatment of AD. However, current PPARγ-targeting drugs such as thiazolidinediones (TZDs) are associated with undesirable side effects. We identified herbal extract with a small molecular, astragaloside IV (AS-IV), as a selective PPARγ natural agonist in nervous cells by developing a PPAR-PPRE pathway regulatory system. Cultured SH-SY5Y cells transfected with pEGFP-N1-BACE1 were treated with AS-IV for 24 h or AS-IV plus the PPAR-γ antagonist GW9662 in vitro. APP/PS1 mice were intragastrically treated with AS-IV or AS-IV plus the GW9662 every 48 h for 3 months. Immunofluorescence, western blotting, and real-time PCR were used to examine the expression of PPARγ and BACE1. Immunohistochemical staining was performed to analyze the distribution of Aβ plaques in the APP/PS1 mouse brain. The levels of Aβ were determined using ELISA kits. AS-IV was shown to be a PPARγ agonist by establishing a high-throughput screening model for PPARγ agonists. The results showed that AS-IV treatment increased activity of PPARγ and inhibited BACE1 in vitro. As a result, Aβ levels decreased significantly. GW9662, which is a PPARγ antagonist, significantly blocked the beneficial role of AS-IV. In vivo, AS-IV treatment increased PPARγ and BACE1 expression and reduced neuritic plaque formation and Aβ levels in the brains of APP/PS1 mice. These effects of AS-IV could be effectively inhibited by GW9662. These results indicate that AS-IV may be a natural PPARγ agonist that suppressed activity of BACE1 and ultimately attenuates generation of Aβ. Therefore, AS-IV may be a promising agent for modulating Aβ-related pathology in AD. [ABSTRACT FROM AUTHOR]

The newly discovered alkali-doped iron selenide superconductors not only reach a superconducting transition temperature as high as 32?K, but also exhibit unique characteristics that are absent from other iron-based superconductors, such as antiferromagnetically ordered insulating phases, extremely high Néel transition temperatures and the presence of Fe vacancies and ordering. These features have generated considerable excitement as well as confusion, regarding the delicate interplay between Fe vacancies, magnetism and superconductivity. Here we report on molecular beam epitaxy growth of high-quality KxFe2?ySe2 thin films and in situ low-temperature scanning tunnelling microscope measurement of their atomic and electronic structures. We demonstrate that a KxFe2?ySe2 sample contains two distinct phases: an insulating phase with well-defined order of Fe vacancies, and a superconducting KFe2Se2 phase containing no Fe vacancies. An individual Fe vacancy can locally destroy superconductivity in a similar way to a magnetic impurity in conventional superconductors. Measurement of the magnetic-field dependence of the Fe-vacancy-induced bound states reveals a magnetically related bipartite order in the tetragonal iron lattice. These findings elucidate the existing controversies on this new superconductor and provide atomistic information on the interplay between magnetism and superconductivity in iron-based superconductors. [ABSTRACT FROM AUTHOR]

We use inelastic neutron scattering to study the low-energy spin excitations of polycrystalline samples of nonsuperconducting CeFeAsO and superconducting CeFeAsO0.84F0.16. Two sharp dispersionless modes are found at 0.85 and 1.16 meV in CeFeAsO below the Ce antiferromagnetic (AF) ordering temperature of T ˜ 4 K. On warming to above T ˜ 4 K, these two modes become one broad dispersionless mode that disappears just above the Fe ordering temperature T ˜ 140 K. For superconducting CeFeAsO0.84F0.16, where Fe static AF order is suppressed, we find a weakly dispersive mode center at 0.4 meV that may arise from short-range Ce-Ce exchange interactions. Using a Heisenberg model, we simulate powder-averaged Ce spin wave excitations. Our results show that we need both Ce spin wave and crystal electric field excitations to account for the whole spectra of low-energy spin excitations. [ABSTRACT FROM AUTHOR]