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光氧化作为一种通过增强淀粉样蛋白清除来治疗神经退行性蛋白病的新策略。

Photo-Oxygenation as a New Therapeutic Strategy for Neurodegenerative Proteinopathies by Enhancing the Clearance of Amyloid Proteins.

作者信息

Tomizawa Ikumi, Nakagawa Hanako, Sohma Youhei, Kanai Motomu, Hori Yukiko, Tomita Taisuke

机构信息

Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.

Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.

出版信息

Front Aging Neurosci. 2022 Jun 23;14:945017. doi: 10.3389/fnagi.2022.945017. eCollection 2022.

Abstract

Alzheimer disease (AD) is associated with the aggregation of two amyloid proteins: tau and amyloid-β (Aβ). The results of immunotherapies have shown that enhancing the clearance and suppressing the aggregation of these two proteins are effective therapeutic strategies for AD. We have developed photocatalysts that attach oxygen atoms to Aβ and tau aggregates light irradiation. Photo-oxygenation of these amyloid aggregates reduced their neurotoxicity by suppressing their aggregation both and . Furthermore, photo-oxygenation enhanced the clearance of Aβ in the brain and microglial cells. Here, we describe the effects of photo-oxygenation on tau and Aβ aggregation, and the potential of photo-oxygenation as a therapeutic strategy for AD, acting microglial clearance.

摘要

阿尔茨海默病(AD)与两种淀粉样蛋白的聚集有关:tau蛋白和淀粉样β蛋白(Aβ)。免疫疗法的结果表明,增强这两种蛋白的清除并抑制其聚集是治疗AD的有效策略。我们已经开发出了光催化剂,在光照下能将氧原子附着到Aβ和tau聚集体上。这些淀粉样聚集体的光氧化通过抑制其聚集在体内和体外均降低了它们的神经毒性。此外,光氧化增强了大脑和小胶质细胞中Aβ的清除。在此,我们描述了光氧化对tau和Aβ聚集的影响,以及光氧化作为一种通过小胶质细胞清除作用来治疗AD的策略的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca0b/9259952/6aa1bbf55d9a/fnagi-14-945017-g0001.jpg

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