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玫瑰红苯并二氮杂菲体外抑制阿尔茨海默病β-淀粉样蛋白聚集。

Photo-induced inhibition of Alzheimer's β-amyloid aggregation in vitro by rose bengal.

机构信息

KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea; Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.

KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea; Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.

出版信息

Biomaterials. 2015 Jan;38:43-9. doi: 10.1016/j.biomaterials.2014.10.058. Epub 2014 Nov 11.

Abstract

The abnormal aggregation of β-amyloid (Aβ) peptides in the brain is a major pathological hallmark of Alzheimer's disease (AD). The suppression (or alteration) of Aβ aggregation is considered to be an attractive therapeutic intervention for treating AD. We report on visible light-induced inhibition of Aβ aggregation by xanthene dyes, which are widely used as biomolecule tracers and imaging markers for live cells. Among many xanthene dyes, rose bengal (RB) under green LED illumination exhibited a much stronger inhibition effect upon photo-excitation on Aβ aggregation than RB under dark conditions. We found that RB possesses high binding affinity to Aβ; it exhibits a remarkable red shift and a strong enhancement of fluorescence emission in the presence of Aβ. Photo-excited RB interfered with an early step in the pathway of Aβ self-assembly and suppressed the conformational transition of Aβ monomers into β-sheet-rich structures. Photo-excited RB is not only effective in the inhibition of Aβ aggregation, but also in the reduction of Aβ-induced cytotoxicity.

摘要

β-淀粉样蛋白(Aβ)肽在大脑中的异常聚集是阿尔茨海默病(AD)的主要病理标志。抑制(或改变)Aβ聚集被认为是治疗 AD 的一种有吸引力的治疗干预措施。我们报告了吖啶染料对 Aβ聚集的可见光诱导抑制作用,吖啶染料被广泛用作生物分子示踪剂和活细胞成像标记物。在许多吖啶染料中,与黑暗条件下相比,绿光 LED 照射下的玫瑰红(RB)对 Aβ聚集的光激发表现出更强的抑制作用。我们发现 RB 与 Aβ具有高结合亲和力;在存在 Aβ的情况下,它表现出显著的红移和荧光发射的强烈增强。光激发的 RB 干扰了 Aβ 自组装途径的早期步骤,并抑制了 Aβ 单体向富含β-折叠结构的构象转变。光激发的 RB 不仅有效抑制 Aβ聚集,而且减少 Aβ 诱导的细胞毒性。

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