Taming Alzheimer's Disease: Graphene Oxide Offers Hope

Alzheimer's disease is an incurable brain illness that causes dementia and mortality in both sufferers and their families (1^✔ ✔Trusted Source
Alzheimer Disease

Go to source). Over 55 million people worldwide are thought to be living with the disease or a comparable form of dementia (2^✔ ✔Trusted Source
Dementia statistics

Go to source). The global cost of Alzheimer's disease is projected to be 1% of the global GDP (3^✔ ✔Trusted Source
The economic burden of dementia in low- and middle-income countries (LMICs): a systematic review

Go to source). The underlying cause of Alzheimer's disease is thought to be misfolded amyloid-beta peptides, or A peptides, that collect and clump in the brain. They cause a chain reaction of damaging processes in neurons (brain cells), resulting in the loss of many critical cell activities or cell death, and consequently a loss of brain function in the affected area. There are currently no viable treatments for amyloid buildup in the brain.

Researchers at Chalmers University of Technology have discovered that treating yeast cells with graphene oxide reduces the quantities of aggregated amyloid peptides (4^✔ ✔Trusted Source
Graphene Oxide Attenuates Toxicity of Amyloid-β Aggregates in Yeast by Promoting Disassembly and Boosting Cellular Stress Response

Go to source).

"This effect of graphene oxide has recently also been shown by other researchers, but not in yeast cells," says Xin Chen, Researcher in Systems Biology at Chalmers and first author of the study. "Our study also explains the mechanism behind the effect. Graphene oxide affects the metabolism of the cells, in a way that increases their resistance to misfolded proteins and oxidative stress. This has not been previously reported."

Advertisement

Investigating the Mechanisms of Alzheimer's Disease Using Baker's Yeast

In Alzheimer's disease, amyloid aggregates cause different cellular metabolic abnormalities, such as stress in the endoplasmic reticulum – a crucial component of the cell that produces many of its proteins. This can impair cells' ability to manage misfolded proteins, leading to an increase in their accumulation.

The aggregates also have an impact on the operation of the mitochondria, which are the cell's powerhouses. As a result, the neurons are subjected to increased oxidative stress (reactive molecules known as oxygen radicals that destroy other molecules), to which brain cells are particularly sensitive.

The investigation was carried out by the Chalmers researchers using a combination of protein analysis (proteomics) and follow-up experiments. They used Saccharomyces cerevisiae yeast as an in vivo model for human cells. Both cell types have processes for managing protein quality that are extremely similar. The study team previously produced this yeast cell model to simulate human neurons afflicted by Alzheimer's disease.

"The yeast cells in our model resemble neurons affected by the accumulation of amyloid-beta42, which is the form of amyloid peptide most prone to aggregate formation," says Xin Chen. "These cells age faster than normal, show endoplasmic reticulum stress and mitochondrial dysfunction, and have elevated production of harmful reactive oxygen radicals."

Advertisement

Graphene Oxide Nanoflakes Have High Hopes

Graphene oxide nanoflakes are two-dimensional carbon nanomaterials with distinctive features such as excellent conductivity and biocompatibility. They are widely employed in a variety of research initiatives, such as the development of cancer treatments, drug delivery systems, and biosensors.

The nanoflakes are hydrophilic (soluble in water) and interact well with biomolecules like proteins. When graphene oxide enters living cells, it can interfere with protein self-assembly processes.

"As a result, it can hinder the formation of protein aggregates and promote the disintegration of existing aggregates," says Santosh Pandit, Researcher in Systems Biology at Chalmers and co-author of the study. "We believe that the nanoflakes act via two independent pathways to mitigate the toxic effects of amyloid-beta42 in the yeast cells."

Graphene oxide acts directly to prevent amyloid-beta42 formation in one pathway. In the other case, graphene oxide acts indirectly through a (now unknown) mechanism that activates certain genes for stress response. This improves the cell's resistance to misfolded proteins and oxidative damage.

The future treatment of Alzheimer's sufferers remains a mystery. According to the Chalmers research group, graphene oxide has enormous potential for future research in the field of neurological illnesses. In a yeast model, the research team has already demonstrated that treatment with graphene oxide lowers the harmful effects of protein aggregation, particularly in Huntington's disease.

"The next step is to investigate whether it is possible to develop a drug delivery system based on graphene oxide for Alzheimer's disease," says Xin Chen. "We also want to test whether graphene oxide has beneficial effects in additional models of neurodegenerative diseases, such as Parkinson's disease."

Advertisement

Proteins and Peptides in the Brain

Proteins and peptides are both made up of amino acids and are fundamentally the same sort of molecule. Peptide molecules are smaller and less intricate in structure, often containing less than 50 amino acids. Proteins and peptides can both become distorted if they fold incorrectly during cell development. When a large number of amyloid-beta peptides clump together in the brain, the aggregates are classed as proteins.

References:

1. Alzheimer Disease - (https://pubmed.ncbi.nlm.nih.gov/29763097/)
2. Dementia statistics - (https://www.alzint.org/about/dementia-facts-figures/dementia-statistics/)
3. The economic burden of dementia in low- and middle-income countries (LMICs): a systematic review - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981345/)
4. Graphene Oxide Attenuates Toxicity of Amyloid-β Aggregates in Yeast by Promoting Disassembly and Boosting Cellular Stress Response - (https://onlinelibrary.wiley.com/doi/full/10.1002/adfm.202304053)

Source-Medindia