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Fraser, S. P.,Suh, Y.-H.,Chong, Y. H.,Djamgoz, M. B. A. 이화여자대학교 생명과학연구소 1996 생명과학연구논문집 Vol.7 No.-
There is mounting evidence that at least some of the neurotoxicity associated with Alzheimer's disease(AD)is due to proteolytic fragments of the β-amyloid precursor protein(βAPP). Most research has focused on the amyloid β protein(Aβ), which has been shown to possess ion channel activity. However, the possible role of other cleaved products of the βAPP is less clear. We have investigated the ability of various products of βAPP to induce membrane ion currents by applying them to Xenopus oocytes, a model system used extensively for investigating electrophysiological aspects of cellular, including neuronal, signalling. We focussed on the 105-amino-acid C-terminal fragment(CT_105)(containing the full sequence Aβ), Which has previously been found to be toxic to cells, although little is known about its mode of action. We have found that CT_105 is exceedingly potent, with a threshold concentration of 100-200nM, in inducing nonselective ion currents when applied from either outside or inside the oocyte and is more effective than either βAPP or the Aβ fragments, β_25-35 or β_1-40. The ion channel activity of CT_105 was concentration dependent and blocked by a monoclonal antibody to Aβ. These results suggest the possible involvememnt of CT_105 in inducing the neural toxicity characteristic of AD.
SUH, YOO-HUN,CHONG, YOUNG HAE,KIM, SEONG-HUN,CHOI, WOONG,MIN, KYEONGSIK,JEONG, SUNG-JIN,FRASER, S. P.,DJAMGOZ, M. B. A. 이화여자대학교 생명과학연구소 1996 생명과학연구논문집 Vol.7 No.-
APP may be associated with defense mechanisms in the central nervous system involving the immune system.^1 The finding of low levels of APP was initially described in proportion to lymphocytes.^2 We examined APP expression in human lymphocytes and spleen and compared APP expression in lymphocytes from Alzheimer's patients to that in lymphocytes from age-matched controls. In spleen, the majority of cells showing A? immunoreactivity was found in the T cell-dependent zone. Fluorescence activated cell sort analysis(FACS) indicated that around 90% of CD4^+ T cells and 60% of CD8^+ T cells were immunoreactive to A? specific monoclonal antibody (mAb) 4G8. Northern blot analysis showed that lymphocyte APP mRNA was gradually increased to reach a maximum at 3 days