The toxic proteins that build up in the brain of patients with Alzheimer’s disease are thought to be responsible for the debilitating disease could be treated with “nanoflakes” of graphene oxide.
This is the conclusion of a team of researchers from Denmark and Sweden, who demonstrated the potential of this treatment approach in a yeast cell model.
There are over 900,000 people living with dementia in the UK and this is set to rise to over one million by 2025.
In people with Alzheimer’s, a faulty blood–brain barrier prevents glucose from reaching the brain, stopping the clearing away of misfolded proteins known as amyloid beta peptides.
These peptides then clump together, forming plaques that collect between neurons and can disrupt cell function, cause chronic inflammation, and even cell death.
To date, there are no effective strategies to combat amyloid accumulation in the brain — but the new findings hint at a potential approach.
The study was undertaken by systems biologist Dr Xin Chen of the Chalmers University of Technology in Gothenburg, Sweden, and her colleagues.
Dr Chen said: “This effect of graphene oxide has recently also been shown by other researchers, but not in yeast cells.
“Our study also explains the mechanism behind the effect. This had not been previously reported.
“Graphene oxide affects the metabolism of the cells in a way that increases their resistance to misfolded proteins and oxidative stress.”
The team explained that the amyloid build-seen ups in Alzheimer’s disease cause harm via various cellular metabolic disorders — such as by causing stress in the “endoplasmic reticulum”, the part of the cell in which proteins are produced.
This reduces cells’ ability to handle misfolded proteins, which in turn increases the accumulation of the amyloid beta peptides, creating a vicious circle.
Alongside this, the aggregates also impair the function of the mitochondria, the “powerhouses” of cells, causing neurons to be exposed to more damage via oxidative stress. Brain cells are particularly sensitive to this kind of harm.
The yeast species used in the researcher’s experiment — Saccharomyces cerevisiae — employs similar mechanisms for controlling protein quality to human cells, making it an appropriate stand-in that mimics how human neurons are affected by Alzheimer’s.
Dr Chen explained: “The yeast cells in our model resemble neurons affected by the accumulation of amyloid beta 42, which is the form of amyloid peptide most prone to aggregate formation.
“These cells age faster than normal, slow endoplasmic reticulum stress and mitochondrial dysfunction, and have elevated production of harmful reactive oxygen radicals.”
The graphene nanoflakes the team have been experimenting with are two-dimensional structures with various unique properties — including outstanding conductivity, water solubility and high biocompatibility.
That said, however, when graphene oxide enters living cells, it serves to interfere with the self-assembly process of proteins.
Paper co-author Dr Santosh Pandit — a fellow Chalmers systems biologist — said: “As a result, it can hinder the formation of protein aggregates and promote the disintegration of existing aggregates.
“We believe that the nanoflakes act via two independent pathways to mitigate the toxic effects of amyloid-beta 42 in the yeast cells.”
One of these pathways involve the direct prevention of amyloid-beta 42 accumulation, while the other involves an indirect — and presently unclear — mechanism by which genes for stress response are activated in the cells, increasing their ability to handle both misfolded protein and oxidative stress.
Dr Chen concluded: “The next step is to investigate whether it is possible to develop a drug delivery system — based on graphene oxide — for Alzheimer’s disease.
“We also want to test whether graphene oxide has beneficial effects in additional models of neurodegenerative diseases, such as Parkinson’s disease.”
The full findings of the study were published in the journal Advanced Functional Materials.
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