Scientists at Chalmers University of Technology have now shown that treatment with graphene oxide results in decreased levels of aggregated amyloid peptides in a yeast cell model.
” This effect of graphene oxide has actually just recently also been revealed by other researchers, but not in yeast cells,” says Xin Chen, Researcher in Systems Biology at Chalmers and very first author of the research study. Graphene oxide affects the metabolic process of the cells, in a way that increases their resistance to misfolded proteins and oxidative stress.
Proteins and Peptides
Proteins and peptides can both end up being warped if they fold in the incorrect method throughout formation in the cell. When many amyloid-beta peptides accumulate in the brain, the aggregates are classified as proteins.
Experiments and mechanisms
In Alzheimers illness, the amyloid aggregates apply their neurotoxic impacts by causing various cellular metabolic conditions, such as tension in the endoplasmic reticulum– a huge part of the cell, in which a lot of its proteins are produced. This can minimize cells capability to deal with misfolded proteins, and subsequently increase the accumulation of these proteins.
The aggregates likewise affect the function of the mitochondria, the cells powerhouses. The nerve cells are exposed to increased oxidative tension (reactive particles called oxygen radicals, which damage other particles); something to which brain cells are particularly sensitive.
They have utilized bakers yeast, Saccharomyces cerevisiae, as an in vivo model for human cells. Both cell types have really comparable systems for managing protein quality.
” The yeast cells in our design look like nerve cells impacted by the accumulation of amyloid-beta42, which is the type of amyloid peptide most prone to aggregate development,” says Xin Chen. “These cells age much faster than typical, show endoplasmic reticulum tension and mitochondrial dysfunction, and have raised production of hazardous reactive oxygen radicals.”
Graphene Oxide Nanoflakes: A Promising Tool
Graphene oxide nanoflakes are two-dimensional carbon nanomaterials with distinct homes, consisting of impressive conductivity and high biocompatibility. They are used thoroughly in numerous research study projects, consisting of the development of cancer treatments, drug shipment systems, and biosensors.
The nanoflakes are hydrophilic (water soluble) and communicate well with biomolecules such as proteins. When graphene oxide enters living cells, it has the ability to disrupt the self-assembly procedures of proteins.
” As a result, it can prevent the development of protein aggregates and promote the disintegration of existing aggregates,” says Santosh Pandit, Researcher in Systems Biology at Chalmers and co-author of the research study. “We think that the nanoflakes act through two independent paths to alleviate the poisonous effects of amyloid-beta42 in the yeast cells.”
In one pathway, graphene oxide acts straight to avoid amyloid-beta42 accumulation. In the other, graphene oxide acts indirectly by a (presently unknown) mechanism, in which specific genes for tension response are triggered. This increases the cells capability to manage misfolded proteins and oxidative stress.
Future Perspectives
How to treat Alzheimers clients is still a question for the future. However, according to the research group at Chalmers, graphene oxide holds fantastic possible for future research study in the field of neurodegenerative diseases. The research study group has already had the ability to show that treatment with graphene oxide likewise minimizes the hazardous effects of protein aggregates particular to Huntingtons disease in a yeast model.
” The next step is to examine whether it is possible to establish a drug delivery system based on graphene oxide for Alzheimers disease,” states Xin Chen. “We also desire to evaluate whether graphene oxide has useful effects in extra models of neurodegenerative illness, such as Parkinsons illness.”
Referral: “Graphene Oxide Attenuates Toxicity of Amyloid-β Aggregates in Yeast by Promoting Disassembly and Boosting Cellular Stress Response” by Xin Chen, Santosh Pandit, Lei Shi, Vaishnavi Ravikumar, Julie Bonne Køhler, Ema Svetlicic, Zhejian Cao, Abhroop Garg, Dina Petranovic and Ivan Mijakovic, 07 July 2023, Advanced Functional Materials.DOI: 10.1002/ adfm.202304053.
The study has actually been carried out in the Mijakovic lab at the Division of Systems and Synthetic Biology at Chalmers University of Technology, and at Technical University of Denmark (DTU). Authors are Xin Chen, Santosh Pandit, Lei Shi, Zhejian Cao, Dina Petranovic and Ivan Mijakovic at Chalmers, and Vaishnavi Ravikumar, Julie Bonne Køhler, Ema Svetlicic and Abhroop Garg at DTU.
The research study has been supported by grants from Vinnova Center CellNova, Novo Nordisk Foundation, Marie Skłodowska-Curie grant, and the Swedish Research Council.
Graphene oxide (orange) can effectively enter yeast cells and lower the toxicity of damaging protein aggregates (light grey), by promoting disassembly and then degradation of the aggregates. Researchers at Chalmers University of Technology, Sweden, have now shown that yeast cells that collect these misfolded amyloid peptides can recover after being treated with graphene oxide nanoflakes.
They set off a series of hazardous processes in the neurons (brain cells)– triggering the loss of many vital cell functions or cell death, and hence a loss of brain function in the afflicted area.” This result of graphene oxide has actually just recently also been revealed by other researchers, but not in yeast cells,” states Xin Chen, Researcher in Systems Biology at Chalmers and very first author of the research study. Graphene oxide impacts the metabolism of the cells, in a way that increases their resistance to misfolded proteins and oxidative stress.
Graphene oxide (orange) can efficiently go into yeast cells and minimize the toxicity of damaging protein aggregates (light grey), by promoting disassembly and then degradation of the aggregates. (not shown by the illustration), graphene oxide treatment can change the metabolism of the cells to increase their capacity to cope with stress.
A probable early chauffeur of Alzheimers disease is the build-up of particles called amyloid peptides. These cause cell death, and are frequently discovered in the brains of Alzheimers patients. Researchers at Chalmers University of Technology, Sweden, have actually now shown that yeast cells that accumulate these misfolded amyloid peptides can recover after being treated with graphene oxide nanoflakes.
Alzheimers disease is an incurable brain disease, resulting in dementia and death, that triggers suffering for both the clients and their households. It is estimated that over 40 million individuals worldwide are dealing with the illness or an associated kind of dementia. According to Alzheimers News Today, the approximated international expense of these diseases is one percent of the international gross domestic item.
Misfolded amyloid-beta peptides, Aβ peptides, that accumulate and aggregate in the brain, are thought to be the underlying cause of Alzheimers disease. They trigger a series of harmful processes in the nerve cells (brain cells)– causing the loss of lots of crucial cell functions or cell death, and therefore a loss of brain function in the affected area. To date, there are no efficient techniques to treat amyloid accumulation in the brain.