Mitsuru Kakihana

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We discovered a nonpeptidic compound, TAK-070, that inhibited BACE1, a rate-limiting protease for the generation of Abeta peptides that are considered causative for Alzheimer's disease (AD), in a noncompetitive manner. TAK-070 bound to full-length BACE1, but not to truncated BACE1 lacking the transmembrane domain. Short-term oral administration of TAK-070(More)
The neurotrophic activity of astrocytes and fibroblasts and its regulation by various cytokines were investigated. Astrocyte conditioned medium (ACM) enhanced the survival of neurons and the proliferation of astrocytes in embryonic cortical cultures grown in serum-free defined medium. However, these results were not affected by acidic fibroblast growth(More)
A novel compound, TDN-345, not bearing catechol moiety, induced NGF synthesis/secretion in C6-10A glioma cells. Both intracellular and extracellular nerve growth factor (NGF) protein levels increased within 3 h and reached a maximum around 12 h after the addition of TDN-345. The induction of NGF synthesis/secretion by TDN-345 occurred in a(More)
The biological activities of recombinant human nerve growth factor (rhNGF) produced by Chinese hamster ovary (CHO) cells that were transfected with human NGF gene were investigated in vitro and in vivo. rhNGF showed the same immunoreactivity as mouse NGF (mNGF) in a highly sensitive two-site enzyme immunoassay system employing mouse monoclonal antibody(More)
We have previously reported the marked increase in plasma levels of endothelin-1 in patients with acute myocardial infarction (AMI). To investigate the effects of severe myocardial ischemia on the production of endothelin-1, plasma concentrations of endothelin-1 were measured by a sandwich-type enzyme immunoassay that we developed recently in both the(More)
Recombinant human basic fibroblast growth factor (rhbFGF) was found to induce secretion of nerve growth factor (NGF) in cultured astrocytes from rat brain. The induction was concentration dependent; a maximum increase of 2-fold was observed at concentrations of 3-10 ng/ml or rhbFGF. When rhbFGF was added to the astrocytes, the induction occurred within 8 h(More)
Idebenone, 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone, at a dose of 100 mg/kg (i.p.) markedly increased the level of 5-hydroxyindole-3-acetic acid (5-HIAA) in several brain regions without affecting monoamine contents in normal rats. In rats with cerebral ischemia, idebenone (10 mg/kg, i.p.) normalized the decreased levels of 5-HIAA in the(More)
Cerebral ischemia was induced by a 200-s occlusion of both common carotid arteries in rats in which both vertebral arteries had been permanently cauterized. In the ischemic rats, a significant decrease in acetylcholine (ACh) and a marked increase in choline were observed in the cerebral cortex, hippocampus, striatum, and diencephalon. A slight increase in(More)
The effects of 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone, CV-2619) on the contents, turnover, release and uptake of monoamines, especially serotonin (5-HT), in various brain regions of Wistar rats were studied in vivo and in vitro. In normal rats, an intraperitoneal (i.p.) dose of 100 mg/kg of CV-2619 had no significant effect(More)
The concentrations of acetylcholine (Ach) and choline in various brain regions of rats with and without cerebral ischemia and the effects of 6-(10-hydroxy-decyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone, CV-2619) on the levels of these parameters were investigated. Cerebral ischemia was induced by a 200-sec occlusion of both common carotid(More)
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