Air pollution is made up of several different components including gases, chemical compounds, metals, and tiny particles are known as particulate matter (PM).
Most research has focused on a component of air pollution known as fine particulate matter (PM2.5) are tiny particles that are 40 times smaller than the width of a human hair.
Long-term, exposure as well as short-term exposure to high levels of air pollution, can be hazardous, leading to health conditions that affect the lungs, brain, and heart. Studies suggest that tiny air pollution particles (PM2.5) can enter the brain, and are responsible for various neurodegenerative diseases.
Table of Contents
- What is Parkinson’s Disease?
- The Relationship between Air pollution and Parkinson’s Disease
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What is Parkinson’s Disease?
Parkinson’s disease is a progressive nervous system disorder that affects movement which is the result of the loss of dopamine-producing brain cells.
The motor symptoms of the disease result from the death of cells in the substantia nigra, a region of the midbrain.
Symptoms start gradually, sometimes starting with a barely noticeable tremor in just one hand. Other symptoms include muscle rigidity, tremors, and changes in speech and gait.
The cause of Parkinson’s disease is unknown but believed to involve both genetic and environmental factors.
The exact cause of neuronal depletion is unknown, but it may involve mitochondrial dysfunction, inflammatory reactions, and oxidative stress. Exposure to pesticides, herbicides, and heavy metals was shown to increase PD risk.
The Relationship between Air pollution and Parkinson’s Disease
Exposure to the elevated levels of air pollution is linked with numerous adverse effects on human health. Air pollution exposure has been linked to brain inflammation and oxidative stress, the mechanism that is believed to contribute to the development and progression of PD.
For example, residents of Mexico City, one of the most polluted metropolitan areas in the world, showed evidence of dangerous levels of neuroinflammation, an altered brain innate immune response, and early accumulation of alpha (α)-synuclein (a protein found in the human brain).
In a pilot study in Mexico City, 56% of randomly selected healthy children showed prefrontal white matter with hyperintense lesions another early hallmark in PD pathology. Air pollution is also thought to have neurotoxic effects on brain development.
Several pathogenic mechanisms have been implicated, including dopamine-dependent oxidative stress, mitochondrial dysfunction, excitotoxicity (a process in which the nerve cells are damaged and killed), and proteasomal impairment.
Plasma concentration of urate, a potent antioxidant, has consistently been associated with decreased PD risk and progression. Dietary urate intake is linked with lower risk of PD .
Several epidemiological studies reported a protective effect of non-steroidal anti-inflammatory medications (NSAIDs) on the risk of PD . Intake of vitamin E, a potent dietary antioxidant is also linked to reduced PD risk.
Intake of coffee and caffeine, also known for its antioxidant properties, were associated with a lower PD risk in numerous studies.
1. Oxidative stress is thought to play an important role in dopaminergic neurotoxicity in Parkinson’s disease
Parkinson’s disease (PD) is associated with the selective loss of dopamine (DA) in the brain.
The brain uses dopamine to send a signal between neuron cells and eventually the brain cannot produce enough dopamine.
This loss of DA causes a deregulation in the nerve circuits that lead to the various motor symptoms such as slow movement, resting tremor, rigidity, and postural instability as well as non-motor symptoms such as sleep disturbances, depression, and cognitive deﬁcits.
Scientists propose that defective sequestration of dopamine into vesicles, leading to the generation of oxidative stress in the cytoplasm, is a key event in the demise of dopaminergic neurons in Parkinson’s disease, and might represent a common pathway that underlies both genetic and sporadic forms of the disorder.
Dopamine-induced oxidative stress, impairs the synaptic vesicle (neuron messenger also known as neurotransmitter vesicle) function and misfolding of α-synuclein, due to mutations or to oxidative damage to this protein, might be components in a self-perpetuating vicious cycle that eventually lead to the demise of dopaminergic neurons.
Another proposed pathway that might lead to these events involves impaired vesicular storage (membrane-bound vacuoles to that store’s various chemicals in the cells) of dopamine.
Recent experimental evidence shows that the expression of mutant α-synuclein in a human dopaminergic cell line increases cytoplasmic dopamine levels and raises the levels of superoxide radicals in the cytoplasm.
All these several cellular mechanisms attributed to oxidative stress are implicated in the selective degeneration of dopaminergic neurons thus, leading to PD pathogenesis.
2. Air pollution disrupts the mitochondrial functions in neuronal cells leading to Parkinson’s disease
Mitochondria are highly dynamic organelles which fulfill a plethora of functions.
Apart from their prominent role in energy metabolism, mitochondria are closely involved in various key cellular processes, such as the regulation of calcium homeostasis, stress response, and cell death pathways.
Also, mitochondria are an important source of reactive oxygen species (ROS).
UFPs have a very large surface-to-volume ratio and are not enclosed by membranous organelles called vesicles or vacuoles, which allow them to directly interact with intracellular proteins, organelles such as mitochondria, or DNA.
UFPs could induce an oxidative burst within the membranes of these organelles by interfering with a NADPH-oxidase activity that is crucial to maintaining a healthy level of ROS in the body.
A recent study has shown that exposure to airborne UFPs is associated with mitochondrial damage, as reflected by an increase in the copy number of mitochondrial DNA (mtDNA).
Damaged mitochondria may then contribute to increased oxidative-stress through different ROS production and subsequently overloading the cell with ROSs, or by interfering with cellular antioxidant defense mechanisms.
Mutations or altered expression of certain proteins result in mitochondrial impairment, oxidative stress, and impaired protein.
Environmental toxins impair mitochondrial function, increase the generation of free radicals, and lead to aggregation of proteins.
Mitochondrial dysfunction affects the neuron cells by adding an increase in oxidative stress and a decline in Adenosine Triphosphate (it is a molecule that provides energy) production, leading to damage of intracellular components and to cell death.
Also, neuroinflammatory mechanisms might contribute to the cascade of consequences leading to cell death.
PM and UFPs exposure is associated with damaged mitochondria, as reflected in increased Mitochondrial DNA copy number. Damaged mitochondria may intensify oxidative-stress production and its effects.
It is a well-known fact that Parkinson’s disease probably results from a complex interaction of environmental and genetic factors.
These cases are classified as sporadic and occur in people with no apparent history of the disorder in their family although the cause of these sporadic cases still remains unclear.
Whereas the 15% of the Parkinson’s cases have a family history of this disorder these cases are termed as “Familial cases” caused by pre-existing mutations in certain genes.
It is not fully understood how genetic changes cause Parkinson disease or influence the risk of developing the disorder.
There are studies that link gene mutations to some disruption in the cell machinery that breaks down (degrades) unwanted proteins in dopamine-producing neurons. As a result, un-degraded proteins accumulate, leading to the impairment or death of these cells.
Some mutations may affect the function of mitochondria and can disrupt its natural process. It can throw it into an overproduction of free radicals. Cells normally counteract the effects of free radicals before they cause damage, but mutations can disrupt this process. As a result, free radicals may accumulate and impair or kill dopamine-producing neurons.
The role of environmental exposure, along with genetic risk factors, is still controversial. In most PD cases, disease onset is probably triggered by a complex interaction of many genetic and non-genetic factors, each of which conveys a minor increase in the risk of disease.
Exposure to elevated levels of air pollution is linked to numerous adverse effects on human health like Parkinson’s’ Alzheimer’s, Ischemia, etc.
In the last several years, an interest has grown in understanding whether air pollution might be a risk factor for PD.
Air pollution exposure has been linked to brain inflammation and oxidative stress, processes that are believed to contribute to the development and progression of PD.
There enough studies that suggest even a short-term exposure to air pollution as a risk factor for the neurological disease.
Although each air pollutant has distinct physical or chemical characteristics, and multiple pathways are involved in disease initiation and progression, an inflammatory reaction is a common mechanism through which pollutants cause damage to human organs, including the CNS.
All these studies suggest that there is a strong case for further research into the effect of air pollution on brain health.
Therefore, the control of environmental factors such as air pollution could be a key factor in limiting the predicted increase in the PD cases worldwide.