Tiny pieces of discarded plastics like styrofoam may promote Parkinson’s
Study finds nanoplastics can enter the brain, interact with alpha-synuclein
Nanoplastics — very tiny particles found in the environment when plastic breaks down — that reach a person’s brain can increase the risk of Parkinson’s disease or its progression by prompting the protein alpha-synuclein to clump and turn toxic.
“A recent study found that polystyrene plastic pollution, among a few other types of plastic, circulates in the blood of most adults tested,” the researchers, mostly with Duke University in North Carolina, wrote. “In [lab] models, polystyrene nanoplastics have been reported to accumulate in the brain and penetrate into the parenchyma,” or brain tissue consisting of neurons and the glial cells that support these nerve cells.
As such, “the emergence of micro and nanoplastics in the environment might represent a new toxin challenge with respect to Parkinson’s disease risk and progression,” Andrew West, PhD, a study co-author and professor in the department of pharmacology and cancer biology as Duke, said in a university news release. “This is especially concerning given the predicted increase in concentrations of these contaminants in our water and food supplies.”
The study, “Anionic nanoplastic contaminants promote Parkinson’s disease–associated [alpha]-synuclein aggregation,” was published in Science Advances.
Discarded, tiny pieces of plastic as a risk factor for Parkinson’s
Although the causes of Parkinson’s disease are not fully understood, there’s evidence that exposure to certain toxins or pollutants are disease risk factors. Most studies look at chemicals, pesticides and similar air or water toxins, and few have investigated whether or how nanoplastics may influence Parkinson’s.
With nanoplastic contamination of food and water — particularly from single-use styrofoam, used in packaging and food containers — increasingly common, understanding whether any association exists is critical, the researchers noted.
They specifically wanted to understand how nanoplastics interact with alpha-synuclein. Toxic clumps or fibrils of this protein in the brain are a molecular hallmark of Parkinson’s, and its toxic accumulation is thought to play a central role in driving disease progression.
For this, the scientists used anionic (negatively charged) nanoplastics from polystyrene.
“The increase in polystyrene nanoplastics in the environment … recent detection of polystyrene contaminants in blood, and past reports of anionic polystyrene plastics disrupting and crossing the blood-brain barrier suggest polystyrene nanoplastics as a relevant type of particle to explore for interaction with [alpha]-synuclein,” the researchers wrote.
Both nanoplastics and alpha-synuclein seen to enter neurons in brain
Through a battery of molecular tests, the researchers determined that anionic polystyrene nanoplastics are able to stick to the alpha-synuclein protein — and when they do, it sets the stage for clumps of the alpha-synuclein protein to form. Protein fibrils, in turn, also were able to stick to nanoplastics, promoting further clumping.
Further experiments using cell models showed that both nanoplastic particles and the alpha-synuclein protein are able to enter neurons through a molecular process known as clathrin-dependent endocytosis.
Once inside nerve cells, both nanoplastics and alpha-synuclein are brought to cellular compartments called lysosomes. Lysosomes are commonly called a cell’s “recycling centers” or “garbage disposals,” responsible for breaking down large, complicated molecules into simple components that can be repurposed by the cell.
But the process by which nanoplastics and alpha-synuclein come together in lysosomes gums up the works, preventing lysosomes from efficiently breaking down alpha-synuclein — which spurs more toxic clumping of the protein.
Through experiments in mice, the researchers showed that these same molecular processes could occur in living animals.
The brains of mice were injected with solutions containing alpha-synuclein, nanoplastics, both, or neither. The injection of both alpha-synuclein and nanoplastics led to a notable increase in the number of toxic protein clumps, compared with alpha-synuclein injection alone.
Injecting nanoplastics alone did not lead to alpha-synuclein clumping in most tested mice, but a handful of mice injected with only nanoplastics showed signs of toxic protein clumping. This was not seen in mice injected with a control solution containing neither alpha-synuclein nor nanoplastics.
Collectively, these findings are indicative of a molecular mechanism by which exposure to polystyrene nanoplastics might set the stage for Parkinson’s development.
“While microplastic and nanoplastic contaminants are being closely evaluated for their potential impact in cancer and autoimmune diseases, the striking nature of the interactions we could observe in our models suggest a need for evaluating increasing nanoplastic contaminants on Parkinson’s disease and dementia risk and progression,” West said.
Nanoplastics seen in brain tissue of people with, without Lewy body dementia
Further supporting this idea, the researchers analyzed brain tissue collected from people without a neurological disease or with Lewy body dementia, a type of atypical parkinsonism that, like Parkinson’s disease, is marked by toxic clumps of alpha-synuclein in the brain. Molecular assessments were consistent with the presence of polystyrene nanoplastics in brain tissue from both sample groups.
While the researchers stressed that these analyses weren’t definitive, their data “provide some of the first measurements for these contaminants that might be present as nanoplastics in human brain tissue.”
The scientists called for further studies.
“The robust interaction between [alpha]-synuclein and nanoplastics contaminants, coupled with the preliminary detection of polystyrene pollution in the human brain, may provide a rationale for further exploration related to nanoplastic exposures” as a Parkinson’s risk factor, they wrote.
“The technology needed to monitor nanoplastics is still at the earliest possible stages and not ready yet to answer all the questions we have,” West added. “But hopefully efforts in this area will increase rapidly, as we see what these particles can do in our models.
“If we know what to look out for, we can take the necessary steps to protect ourselves, without compromising all the benefits we reap every day from plastics,” he said.
This work was supported by funding from The Michael J. Fox Foundation for Parkinson’s Research and the Aligning Science Across Parkinson’s initiative.