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cainiaodui新蟲 (小有名氣)
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| Targeting a key step in the generation of amyloidogenic peptides and the proteolytic activation of NOTCH signaling, a number of GSIs are currently in preclinical and clinical development for indications ranging from Alzheimer disease to T-cell acute lymphoblastic leukemia (T-ALL). A major hurdle to the therapeutic development of GSIs has been the on-target toxicity in the gastrointestinal tract. Inhibition of NOTCH signaling results in goblet cell metaplasia due to the skewed differentiation of epithelialcells in the intestinal crypts away from an enterocyte fate and towards that of a secretory goblet cell. Development of goblet cell metaplasia requires simultaneous disruption of both Notch1 and Notch2. Because GSIs indiscriminately block all NOTCH receptors, targeted inhibition of individual receptors might help to alleviate the observed gut toxicity. |
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RXMCDM: 金幣+1, 多謝應(yīng)助！ 2014-03-15 15:00:31
RXMCDM: 金幣+1, 多謝應(yīng)助！ 2014-03-15 15:00:31
| 目標(biāo)的一個(gè)關(guān)鍵步驟的生成amyloidogenic NOTCH信號(hào)肽和蛋白水解激活,大量GSIs目前正在臨床前和臨床發(fā)展的跡象包括阿爾茨海默病、t細(xì)胞急性淋巴細(xì)胞白血病(T-ALL)。GSIs的治療發(fā)展的一個(gè)主要障礙是目標(biāo)在胃腸道毒性。抑制切口信號(hào)導(dǎo)致杯狀細(xì)胞化生由于傾斜分化的epithelialcells腸道隱窩的腸上皮細(xì)胞的命運(yùn)轉(zhuǎn)向分泌的杯狀細(xì)胞。杯狀細(xì)胞化生的發(fā)展需要同時(shí)Notch1和Notch2中斷。因?yàn)镚SIs不分青紅皂白地屏蔽所有切口受體,抑制個(gè)人目標(biāo)受體可能有助于緩解觀察腸毒性。（因?yàn)楸救耸菍W(xué)生化的，有些名詞不懂，請(qǐng)見諒） |
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