Effects of corticosterone and amyloid-beta on proteins essential for synaptic function: Implications for depression and Alzheimer's disease.

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Endoplasmic reticulum stress induces tau pathology and forms a vicious cycle: Implication in Alzheimer's disease pathogenesis

Accumulation of unfolded proteins can disturb the functions of the endoplasmic reticulum (ER), leading to ER-stress or unfolded protein response (UPR). Recent data have shown that activation of UPR can be found in postmortem brains of Alzheimer's disease (AD) patients; and biological markers for activation of UPR are abundant in neurons with diffuse phosphorylated tau. Although these observations suggest a linkage between ER-stress and tau pathology, little is known of their relationship. In this study, we found that high levels of phosphorylated PKR-like ER-resident kinase (p-PERK) and phosphorylated eukaryotic initiation factor 2 alpha (p-eIF2α) as markers for activation of UPR in the hippocampus of aged P301L mutant tau transgenic mice. The immunoreactivity of p-PERK was found to co-localize with that of phosphorylated tau. We then hypothesized that phosphorylation of tau could induce ER-stress and vice versa in promoting AD-like pathogenesis. By using the protein phosphatase 2A inhibitor okadaic acid (OA) as an inducer for phosphorylation of tau, we found that primary cultures of rat cortical neurons treated with OA triggered UPR as indicated by increased levels of p-PERK and p-eIF2α, splicing of mRNA for xbp-1 and elevated levels of mRNA for GADD153. On the other hand, thapsigargin as an ER-stress inducer stimulated phosphorylation of tau at Thr231, Ser262 and Ser396. Thapsigargin also induced activation of caspase-3 and cleavage of tau. These findings suggested that ER-stress and hyperphosphorylation of tau could be induced by each other to form a vicious cycle to propagate AD-like neurodegeneration. © 2012 - IOS Press and the authors. All rights reserved.postprin

A Formal Approach to the Modelling of Digital Archives

Abstract. Understanding digital information for users who have different background knowledge becomes important for archival information systems. Key challenges include contextual knowledge changing over time and across different designated communities, and the lack of the reference knowledge among them. Therefore, in order to help users understand digital archives precisely, an archival system should preserve its resources along with their underlying community knowledge, and support the interpretation of their concepts in the right context together with relevant concepts. This research presents a formal approach to digital archives including ontology for preserving the evolution of contextual knowledge. In addition, a prototype has been developed to demonstrate the feasibility and suitability of the proposed formal approach. It is found that the proposed approach can serve as a framework to enhance the capability of the existing archival information systems with regard to the fulfillment of the need of understanding digital archives

A reciprocal relationship between reactive oxygen species and mitochondrial dynamics in neurodegeneration

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