Graphene Oxide Attenuates Toxicity of Amyloid-β Aggregates in Yeast by Promoting Disassembly and Boosting Cellular Stress Response
Artikel i vetenskaplig tidskrift, 2023

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.

graphene oxide

misfolded protein

amyloid-β

Alzheimer's disease

oxidative stress

Författare

Xin Chen

Chalmers, Life sciences, Systembiologi

Santosh Pandit

Chalmers, Life sciences, Systembiologi

Lei Shi

Chalmers, Life sciences, Systembiologi

V. Ravikumar

Novo Nordisk Fonden

Julie Bonne Køhler

Novo Nordisk Fonden

Ema Svetlicic

Novo Nordisk Fonden

Zhejian Cao

Chalmers, Life sciences, Systembiologi

Abhroop Garg

Novo Nordisk Fonden

Dina Petranovic Nielsen

Chalmers, Life sciences, Systembiologi

Novo Nordisk Fonden

Ivan Mijakovic

Novo Nordisk Fonden

Chalmers, Life sciences, Systembiologi

Advanced Functional Materials

1616-301X (ISSN) 16163028 (eISSN)

Vol. 33 45 2304053

Ämneskategorier

Cellbiologi

Biokemi och molekylärbiologi

Neurovetenskaper

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

DOI

10.1002/adfm.202304053

Mer information

Senast uppdaterat

2024-03-07