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用于光触发调节阿尔茨海默病 β-淀粉样蛋白自组装的光敏材料和平台。

Photosensitizing materials and platforms for light-triggered modulation of Alzheimer's β-amyloid self-assembly.

机构信息

Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291, Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.

Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291, Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.

出版信息

Biomaterials. 2019 Jan;190-191:121-132. doi: 10.1016/j.biomaterials.2018.10.043. Epub 2018 Oct 30.

Abstract

The abnormal aggregation of β-amyloid (Aβ) peptides is a hallmark of Alzheimer's disease (AD) that affects more than 10% of the people over the age 60 world-wide. While the exact mechanism of neuronal loss and cognitive decline has not been elucidated yet, the amyloid hypothesis about the causative role of Aβ aggregation in AD pathology has been widely supported by the numerous in vivo and in vitro data. In this respect, many efforts have been made to explore therapeutic agents that can modulate the aggregation of Aβ, but none of the efforts succeeded in producing effective anti-Aβ drugs for treating AD. This article provides an overview of recent attempts that have employed light energy to intervene with the self-assembly process of Aβ peptides via the generation of oxidative stress by photosensitizers, such as natural or synthetic dyes, light-responsive nanomaterials, and photoelectrochemical platforms. The underlying mechanism of photodynamic reactions suppressing Aβ aggregation and the dilemma in generating long-been-blamed oxidative stress are discussed by addressing the positive role of oxidative stress produced by the photosensitizers in the light-induced suppression of Aβ-mediated neurotoxicity. We have summarized current challenges and strategies to advance photo-induced inhibition and modulation of Aβ aggregation as a therapeutic option for treating AD in the future.

摘要

β-淀粉样蛋白(Aβ)肽的异常聚集是阿尔茨海默病(AD)的一个标志,影响着全球超过 60 岁的 10%以上的人。虽然神经元丧失和认知能力下降的确切机制尚未阐明,但 Aβ 聚集在 AD 病理中的致病作用的淀粉样蛋白假说得到了大量体内和体外数据的广泛支持。在这方面,人们已经做出了许多努力来探索可以调节 Aβ聚集的治疗剂,但没有一种努力成功地生产出有效的抗 Aβ 药物来治疗 AD。本文概述了最近的一些尝试,这些尝试利用光能通过光敏剂(如天然或合成染料、光响应纳米材料和光电化学平台)产生的氧化应激来干预 Aβ 肽的自组装过程。通过解决光敏剂产生的氧化应激在光诱导抑制 Aβ 介导的神经毒性中的积极作用,讨论了光动力反应抑制 Aβ 聚集的潜在机制以及产生长期以来备受指责的氧化应激的困境。我们总结了目前的挑战和策略,以推进光诱导抑制和调节 Aβ 聚集作为治疗 AD 的一种治疗选择。

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