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OBJECTIVE High level of homocysteine (Hcy) is a recognized risk factor for developing Alzheimer disease (AD). However, the mechanisms involved are unknown. Previously, it was shown that high Hcy increases brain β-amyloid (Aβ) levels in amyloid precursor protein transgenic mice, but no data are available on the effect that it may have on the other main(More)
We previously observed that (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide (U50,488H) promoted internalization and phosphorylation of the FLAG-tagged human kappa opioid receptor (FLAG-hkor) stably expressed in Chinese hamster ovary (CHO) cells. In this study, we compared regulation of the FLAG-hkor expressed in CHO cells by(More)
The agonist (-)(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidiny)-cyclohexyl]benzeneacetamide [(-)U50,488H] caused desensitization of the human kappa-opioid receptor (hkor) and Flag-tagged hkor (Flag-hkor) but not the rat kappa-opioid receptor (rkor) and Flag-tagged rkor (Flag-rkor) stably expressed in CHO cells as assessed by guanosine(More)
BACKGROUND Intracellular deposition of tau protein is a hallmark lesion of Alzheimer's disease. Although it is known this event is secondary to excessive tau phosphorylation, the mechanisms involved remain unknown. We previously reported that the enzyme 5-Lipoxygenase (5LO) acts as a modulator of Aβ peptides formation in vivo, and here we investigate its(More)
The formation of Aβ is directly controlled by the γ-secretase complex and its activator, γ-secretase activating protein (GSAP). GSAP derives from a C-terminal fragment of a larger precursor protein via a caspase-3 mediated cleavage. However, the mechanism regulating this process remains unknown. Here we provide in vitro experimental evidence that(More)
BACKGROUND A major feature of Alzheimer's disease (AD) is the accumulation of amyloid-beta (Aβ), whose formation is regulated by the gamma-secretase complex and its activating protein (also known as GSAP). Because GSAP interacts with gamma-secretase without affecting the cleavage of Notch, it is an ideal target for a viable anti-Aβ therapy. However, despite(More)
Using drugs acting on nicotinic acetylcholine receptors (nAChRs), we examined temporal-parietal and frontal cortex, hippocampus, and cerebellum to identify sites of cognition enhancement in 4- and 27-month rabbits. First, we compared radioligand receptor binding for neuronal alphabeta heteromeric nAChRs ([3H]epibatidine) and alpha7 homomeric nAChRs(More)
Neuronal alphabeta heteromeric and alpha7 homomeric nicotinic acetylcholine receptors (nAChRs) were compared in 4- and 27-month rabbits selected for learning proficiency. Sixty 4- and 60 27-month rabbits received the alpha7 nAChR agonist (MEM-3389), galantamine, or vehicle during training in trace eyeblink classical conditioning. Brain tissue from the best(More)
Peritoneal metastases are one reason for the poor prognosis of scirrhous gastric cancer (SGC), and myofibroblast provides a favorable environment for the peritoneal dissemination of gastric cancer. The aim of this study was to determine whether myofibroblast originates from peritoneal mesothelial cells under the influence of the tumor microenvironment.(More)