Search

Accumulation of β-amyloid (Aβ) and resultant inflammation are critical pathological features of Alzheimer disease (AD). Microglia, a primary immune cell in brain, ingests and degrades extracellular Aβ fibrils via the lysosomal system. Autophagy is a catabolic process that degrades native cellular components, however, the role of autophagy in Aβ degradation by microglia and its effects on AD are unknown. Here we demonstrate a novel role for autophagy in the clearance of extracellular Aβ fibrils by microglia and in the regulation of the Aβ-induced NLRP3 (NLR family, pyrin domain containing 3) inflammasome using microglia specific atg7knockout mice and cell cultures. We found in microglial cultures that Aβ interacts with MAP1LC3B-II via OPTN/optineurin and is degraded by an autophagic process mediated by the PRKAA1 pathway. We anticipate that enhancing microglial autophagy may be a promising new therapeutic strategy for AD.

A dental Ag–Au–Cu–Pd alloy with small amounts of Zn and Ir was examined to determine the association of the age-hardenability with the phase transformation process and microstructural changes by means of hardness testing, X-ray diffraction study, field emission scanning electron microscopic observation and energy dispersive spectrometry. The fast and apparent age-hardenability of the present alloy was possibly attributed to phase separation by spinodal decomposition and the formation of a fine and coherent cuboidal structure composed of the Ag–Au-rich a1phase and the metastable Cu–Au-rich a2' phase. The lamellar-forming grain boundary reaction was induced by internal strain before the maximum hardness value was obtained. Moreover, growth of the grain boundary lamellar structure toward the grain interior and its coarsening acted as a strain-releasing softening mechanism, which caused a decrease in age-hardenability. A change in Ag and Pd content might alter the start point of lamellar-formation and the age-hardenability of Ag–Au–Cu–Pd alloys.

Abstract: The age-hardening and overaging mechanisms related to the metastable phase formation by the decomposition of Ag and Cu in a dental casting gold alloy composed of 56Au–25Ag–11.8Cu–5Pd–1.7Zn–0.4Pt–0.1Ir (wt.%) were elucidated by characterizing the age-hardening behaviour, phase transformations, changes in microstructure and changes in element distribution. The fast and apparent increase in hardness at the initial stage of the aging process at 400°C was caused by the nucleation and growth of the metastable Ag–Au-rich phase and the Cu–Au-rich phase by the miscibility limit of Ag and Cu. The transformation of the metastable Ag–Au-rich phase into the stable Ag–Au-rich phase progressed concurrently with the ordering of the Cu–Au-rich phase into the AuCu I phase through the metastable state, which resulted in the subsequent increase in hardness. The further increase in hardness was restrained before complete decomposition of the parent α0 phase due to the initiation of the lamellar-forming grain boundary reaction. The progress of the lamellar-forming grain boundary reaction was not directly connected with the phase transformation of the metastable phases into the final product phases. The heterogeneous expansion of the lamellar structure from the grain boundary caused greater softening than the subsequent further coarsening of the lamellar structure. The lamellar structure was composed of the Ag–Au-rich layer which was Cu-, Pd- and Zn-depleted and the AuCu I layer containing Pd and Zn.

Abstract: The complex precipitation mechanisms related to the age-hardening of Cu-free Au-Ag-Pt-Zn-In alloy for multipurpose dental use was studied by means of hardness test, X-ray diffraction (XRD) studies, field emission scanning electron microscopic (FE-SEM) observations, energy dispersive spectrometer (EDS) analysis, and electron probe microanalysis (EPMA). The early diffusion and then clustering of the In-concentrated phase in the grain interior, together with the early diffusion and then ordering of the PtZn phase in the grain boundary, introduced the internal strains in the Au-Ag-rich α1 matrix, resulting in the hardening process. As the Au-Ag-rich α1’ and PtZn β lamellarforming grain boundary reaction progressed, the phase boundaries between the solute-depleted face-centered cubic (FCC) α1’ matrix and the face-centered tetragonal (FCT) PtZn β precipitate reduced, resulting in softening. In the particlelike structures composed of the major Pt-Au-rich α2 phase and the minor Pt-Zn-rich α3 phase, the separation of In and Zn progressed producing the In-increased Pt-Au-rich α2’ phase and the Zn-increased PtZn α3′ phase with aging time without restraining the softening. The miscibility limit by complex systems of Au-Pt, Ag-Pt, Au-In and In-Zn resulted in the phase transformation and related microstructural changes.