全球精选文摘 - 永久带电的低细胞毒性分支多胺通过阻断朊病毒转化从而抑制朊病毒

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永久带电的低细胞毒性分支多胺通过阻断朊病毒转化从而抑制朊病毒

The inhibition of prions through blocking prion conversion by permanently charged branched polyamines of low cytotoxicity

Lim Y-B, Mays CE, Kim Y 2010/7/30 15:42:55

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Biomaterials, 2010,

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Branched polyamines are effective in inhibiting prions in a cationic surface charge density dependent manner. However, toxicity associated with branched polyamines, in general, often hampers the successful application of the compounds to treat prion diseases. Here, we report that constitutively maintained cationic properties in branched polyamines reduced the intrinsic toxicity of the compounds while retaining the anti-prion activities. In prion-infected neuroblastoma cells, quaternization of amines in polyethyleneimine (PEI) and polyamidoamine (PAMAM) dendrimers markedly increased the nontoxic concentration ranges of the compounds and still supported, albeit reduced, an appreciable level of anti-prion activity in clearing prions from the infected cells. Furthermore, quaternized PEI was able to degrade prions at acidic pH conditions and inhibit the in vitro prion propagation facilitated by conversion of the normal prion protein isoform to its misfolded counterpart, although such activities were decreased by quaternization. Quaternized PAMAM was least effective in degrading prions but efficiently inhibited prion conversion with the same efficacy as unmodified PAMAM. Our results suggest that quaternization represents an effective strategy for developing nontoxic branched polyamines with potent anti-prion activity. This study highlights the importance of polyamine structural control for developing polyamine-based anti-prion agents and understanding of an action mechanism of quaternized branched polyamines.

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疾病资源中心

高血压	慢性阻塞性肺病
脂肪性肝病	糖尿病
卒中	肺癌
冠心病	子宫内膜异位症
结直肠癌	乳腺癌
心力衰竭	心律失常

病例分析 [栏目介绍]

甲状腺功能亢进合并黄疸

王燕燕王曙

上海交通大学附属瑞金医院内分泌科

患者，女，69岁。2009年1月无明显诱因下出现乏力，当时程度较轻，未予以重视。2009年3月患者乏力症状加重，尿色逐渐加深，大便习惯改变，颜色变淡。4月18日入我院感染科治疗，诉轻度头晕、心慌，体重减轻10kg。无肝区疼痛，无发热，无腹痛、腹泻、腹胀、里急后重，无恶性、呕吐等。入院半月前于外院就诊，查肝功能：ALT 601IU/L，AST 785IU/L，TBIL 97.7umol/L，白蛋白 41g/L，甲状腺功能：游离T3 30.6pmol/L，游离T4 51.9pmol/L，心电图示快速房颤。

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