From protein misfolding to gut–brain signalling, emerging evidence suggests that everyday plastic exposure may intersect with key biological processes implicated in Parkinson’s disease, raising urgent questions about long-term neurological risk.
Study: Micro-nanoplastics and Parkinson’s disease: evidence and perspectives. Image Credit: AtlasStudio / Shutterstock
In a recent review published in npj Parkinson's Disease, researchers reviewed emerging experimental and mechanistic evidence linking micro- and nanoplastics (MPs/NPs) to the pathogenesis of Parkinson's disease (PD).
The review details how MPs/NPs enter the body, cross the blood-brain barrier, and accumulate in neural tissue, further identifying specific molecular mechanisms, including protein aggregation, mitochondrial dysfunction, neuroinflammation, and gut-brain axis disruption, through which plastics may contribute to neurodegeneration. The review frames MPs/NPs as a potential, emerging environmental hazard and calls for large-scale prospective studies to quantify human disease risk and exposure, outcome relationships.
Rising Parkinson’s Disease Incidence and Environmental Drivers
Parkinson's disease (PD) is a progressively worsening disorder of the neurological system. Reports highlight PD as the second most prevalent neurodegenerative condition globally and warn that its incidence is rising faster than any other neurological disorder.
While a growing body of evidence elucidates the mechanistic contributions of aging and genetics, the explosive growth of PD cases, alarmingly projected to continue rising for the next 30 years, suggests environmental factors are major contributors. One of the leading simultaneous environmental crises today is plastic accumulation.
Human Exposure to Micro- and Nanoplastics
Studies have found that, upon discharge into the environment, plastic debris degrades into microplastics (1 µm to 5 mm) and nanoplastics (<1 µm) due to ultraviolet radiation and physical wear. These particles are ubiquitous in water, air, and food, and estimates suggest humans ingest up to 52,000 particles annually.
Human clinical research has shown that, once inside the body, these minute particles cross biological barriers. They have been detected in human blood, liver, and brain tissue at concentrations as high as 4917 µg/g.
Scope and Objectives of the Review
This narrative review collates recent research on the effects of micro- and nanoplastics on neurobiological processes relevant to Parkinson’s disease, thereby assessing whether the ubiquitous environmental threat posed by plastic particles could plausibly contribute to the rising PD incidence.
Experimental Models and Plastic Types Examined
Review data were obtained from a broad body of preclinical, cell-based, and computational studies across in vivo (animal), in vitro (cell culture), and computational models to map the toxicity of MPs/NPs. The review analyzed how different types of plastics, specifically polystyrene (PS), polyethylene (PE), and polyvinyl chloride (PVC), interact with biological systems.
The review focused on three primary human exposure routes: ingestion, inhalation, and dermal contact. Analyses examined findings from mammalian models, such as C57BL/6J mice, and non-mammalian organisms, such as C. elegans and zebrafish, to determine how plastics traverse the body.
Routes of Brain Entry and Neural Accumulation
The review describes mechanisms by which nanoplastics can penetrate the blood-brain barrier via the circulatory system or bypass it through the olfactory nerve (nose-to-brain) and the vagus nerve (gut-to-brain) axes. Evidence is also discussed linking plastic exposure to key pathological features of PD, including Lewy body formation and dopamine neuron death.
Protein Aggregation and Alpha-Synuclein Pathology
Mechanistic evidence from experimental models suggests that MPs/NPs may promote PD-relevant neurodegenerative processes through multiple intersecting pathways.
Acceleration of protein clumping, the hallmark of PD, is the accumulation of misfolded alpha-synuclein proteins, Lewy bodies. Nanoplastics can interact with hydrophobic regions of these proteins, acting as scaffolds that accelerate aggregation.
In patient-derived cell models, nanoplastics increased alpha-synuclein aggregates by approximately 50%. Plastics also impaired lysosomal function, reducingthe degradation efficiency of toxic fibrils by about 30%.
Gut Barrier Disruption and Neuroinflammation
Oral exposure to plastics damages the intestinal barrier by downregulating tight junction proteins such as ZO-1. This creates a leaky gut, allowing bacterial toxins, including lipopolysaccharide (LPS), and inflammatory cytokines to enter circulation and reach the brain, promoting systemic and neuroinflammation.
Animal studies show chronic exposure to MPs/NPs alters gut microbiome composition, depleting beneficial bacteria and increasing the Firmicutes to Bacteroidetes ratio, a pattern often observed in PD patients.
Mitochondrial Dysfunction and Neuronal Energy Failure
Polystyrene nanoplastics inhibit complex I of the electron transport chain, reducing adenosine triphosphate (ATP) production and increasing oxidative stress. This energy deficit activates the AMP-activated protein kinase/unc-51-like kinase 1 (AMPK/ULK1) pathway, driving excessive mitophagy and ultimately neuronal death.
Excitotoxicity, Metal Dysregulation, and Ferroptosis
Plastics impair astrocyte function by reducing excitatory amino acid transporter 2 (EAAT2) activity, leading to glutamate accumulation and excitotoxicity. Plastics can also transport heavy metals, disrupting iron homeostasis and triggering ferroptosis, an iron-dependent form of cell death implicated in the loss of dopamine-producing neurons.
Implications for Neurodegenerative Disease Risk
This review underscores the biological plausibility of a link between plastic pollution and Parkinson’s disease, identifying MPs and NPs as active agents capable of interacting with pathways central to PD pathology.
By facilitating protein misfolding, impairing mitochondrial function, promoting neuroinflammation, and disrupting the gut-brain axis, MPs/NPs are highlighted as multidimensional experimental risk factors for neurological health. However, current evidence remains largely preclinical and mechanistic. Well-designed prospective human studies integrating environmental exposure assessment with long-term clinical follow-up are required to inform regulatory thresholds and public health strategies.
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