酸化グラフェンがアルツハイマー病タンパク質の毒性を軽減(Graphene oxide reduces the toxicity of Alzheimer’s proteins)

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2023-10-04 チャルマース工科大学

◆アルツハイマー病は治療不可能な脳疾患で、世界中で多くの人々に影響を与えています。この病気の原因はアミロイドベータペプチド(Aβペプチド)の脳内蓄積と考えられています。
◆スウェーデンの研究者たちは、グラフェンオキサイドの治療が酵母細胞モデルでアミロイドペプチドの凝集を減少させる効果があることを示しました。これにより、アルツハイマー病治療への新たな可能性が開かれました。将来的には、グラフェンオキサイドを用いたアルツハイマー病の治療法や他の神経変性疾患への応用が検討されています。

<関連情報>

グラフェン酸化物が酵母のアミロイドβ凝集体の毒性を軽減し、細胞ストレス応答を促進 Graphene Oxide Attenuates Toxicity of Amyloid-β Aggregates in Yeast by Promoting Disassembly and Boosting Cellular Stress Response

Xin Chen, Santosh Pandit, Lei Shi, Vaishnavi Ravikumar, Julie Bonne Køhler, Ema Svetlicic, Zhejian Cao, Abhroop Garg, Dina Petranovic, Ivan Mijakovic
Advanced Functional Materials  Published: 07 July 2023
DOI:https://doi.org/10.1002/adfm.202304053

酸化グラフェンがアルツハイマー病タンパク質の毒性を軽減(Graphene oxide reduces the toxicity of Alzheimer’s proteins)

Abstract

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease, with the aggregation of misfolded amyloid-β (Aβ) peptides in the brain being one of its histopathological hallmarks. Recently, graphene oxide (GO) nanoflakes have attracted significant attention in biomedical areas due to their capacity of suppressing Aβ aggregation in vitro. The mechanism of this beneficial effect has not been fully understood in vivo. Herein, the impact of GO on intracellular Aβ42 aggregates and cytotoxicity is investigated using yeast Saccharomyces cerevisiae as the model organism. This study finds that GO nanoflakes can effectively penetrate yeast cells and reduce Aβ42 toxicity. Combination of proteomics data and follow-up experiments show that GO treatment alters cellular metabolism to increases cellular resistance to misfolded protein stress and oxidative stress, and reduces amounts of intracellular Aβ42 oligomers. Additionally, GO treatment also reduces HTT103QP toxicity in the Huntington’s disease (HD) yeast model. The findings offer insights for rationally designing GO nanoflakes-based therapies for attenuating cytotoxicity of Aβ42, and potentially of other misfolded proteins involved in neurodegenerative pathology.

有機化学・薬学
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