Parkinson’s Disease and How Environmental Toxins Cause Parkinson’s Disease

Parkinson’s disease is a common neurogenic disease, which exists in both sporadic and genetically inherited forms. Most Parkinson’s disorders, accounting for over 95% of all cases, are sporadic (Meulener et al., 2005). The condition is characterized by large motor and non-motor features that have varying degrees of impact on normal brain functioning.

Parkinson’s disease mostly affects older people of over 60 years in age and affects atleast 1% of the older population (Connolly, & Lang, 2014). Since the condition is incurable, patients are usually given therapies to improve their living conditions. However, the pharmacological management of the Parkinson’s motor and non-motor functions has several side effects which include nausea and psychosis that causes hallucinations. These side effects can also be managed through medication.

Signs and Symptoms of Parkinson’s Disease Diagnosis

The disease is diagnosed through a clinical symptoms evaluation criteria as there is no definitive test for the condition. The cardinal signs used to diagnose Parkinson’s disease include:

  • Rest tremor
  • Bradykinesia
  • Loss or rigidity of postural reflexes

In addition to these signs, Parkinson’s disease symptoms like cognitive and neurobehavioral abnormalities as well as glabella reflexes, dystonia, and hypomania are considered as secondary motor symptoms which can be used to diagnose the condition (Jankovic, 2008).

Parkinson’s diagnostics depend on a number of rating scales, which evaluate the degree of the patient’s motor impairment and disability with the disorder. Although the scales used for diagnosis of Parkinson’s disorders have not yet been evaluated for reliability and credibility, they categorize the disorder into stages of progression from stage 0-5. These stages are based on the signs and symptoms presented by the patient.

Etiology and Etiological Causes of Parkinson’s Disease

The etiology of Parkinson’s disease is quite complex, considering that it’s a polygenic disease. Various etiological causes of the disease that are related to genetic and environmental factors affect the pathological development of Parkinson’s disease.

However, while both genetic factors and environmental toxins are attributed to the etiology of Parkinson’s disease, the percentage of monogenic (genetic) mutations linked cases is very low. In other words, most cases, the larger share that constitutes 95% sporadic Parkinson’s disorders, are caused by environmental oxidative toxins.

Environmental Toxins Caused Sporadic Parkinson’s Disease Conditions

Scientific evidence has associated several environmental toxins to Parkinson’s disorder.Toxins like pesticides and heavy metals have been associated with a high risk for sporadic Parkinson’s disorders. Most environmental toxins cause Parkinson’s disease by affecting the normal functioning of cell mitochondria within body cells as a result of their oxidation reaction with cell contents and the eventual oxidative stress.

Toxic Pesticides That Cause Parkinson’s Disorders

Scientists have studied several models to establish the aspects and action mechanisms of various pesticides and herbicides that are linked to sporadic Parkinson’s disease conditions (Nisticò, Mehdawy, Piccirilli, & Mercuri, 2011).

Key pesticides that cause Parkinson’s disease include:

  • Rotenone
  • Paraquat
  • Dieldrin
  • Pyrethroid
Pyrethroid Pesticides

Pyrethroid pesticides are associated with a high risk of developing Parkinson’s disease. Pyrethroid pesticides are synthetic derivatives of natural pyrethrum and include permethrin and deltamethrin that accumulate in the brain causing toxicity.

Paraquat Pesticides

Paraquat pesticides damage plant membranes by interfering with the production of oxygen free radicals and photosynthesis in plants (Breckenridge, et al, 2013). Paraquat pesticide has a similar structure to the MPP+, a dopaminergic neurotoxin, which makes it a potential toxin that increases the risk of Parkinson’s disease. Paraquat increases mitochondria fusion, reducing levels of essential fusion factors.

Deldrin Organochlorine Pesticides

Other pesticides associated with Parkinson’s disorders are organochlorines pesticides such as Dieldrin. Deldrin pesticide has a high half-life of about 25 years that increases the risk of human exposure to the toxin. Deldrin pesticides are therefore easily consumed in food products and their effects are felt upto decades later after the initial exposure to the toxic pesticides.

Heavy Metals That Cause Parkinson’s Disorders

In addition to pesticides, excessive heavy metals such as copper, iron, zinc and manganese are involved in neurodegeneration Parkinson’s disease development by causing the cellular dysfunction of mitochondria and oxidative stress. These cellular respiration dysfunctions increase the risk of developing Parkinson’s disorders. Heavy metal toxin accumulation results in motor impairments and cognitive alterations resembling the symptoms observed in Parkinson’s disease patients.

Toxic Manganese Accumulation in the Body

Manganese has the highest toxic effect on human beings when compared to other heavy metals. This is due to the significant role that it plays in influencing brain development and hemostasis. Manganese is essential for critical enzymatic reactions in the body such as the activation of mitochondria antioxidant defense systems.

However, in excess and depending on its oxidative state, Manganese triggers toxicity and other harmful effects in the brain. The excessive accumulation of Manganese in the brain’s basal ganglia or in the liver is, specifically, associated with a high risk of the SLC30A10 gene mutation that induces Parkinsonism gene expression.

Specific Mechanisms of Pesticide Environmental Toxins

The Mechanism of Rotenone Pesticide Toxicity

Rotenone is a potent non-competitive mitochondria inhibitor which is derived from the Leguminosae family plants (Tanner, et al., 2011). According to Tanner et al, the half-life of Rotenone pesticide is relatively short, at about 3 days. Hence consumption of the toxin through contaminated food, though highly unlikely, affects the people through low chronic exposure.

Rotenone pesticide is a highly lipophilic chemical, altering mitochondrion functions and enhancing mitochondrion fusion. Rotenone pesticide has also been associated with impairing the interactions of mitochondrion transport proteins with neurons. This significantly effects mitochondrion dynamics and neural motor activities as observed in Parkinson’s disease patients.

Rotenone is extremely hydrophobic, which makes it easier to cross biological membranes. The pesticide does not require dopamine transporters to access the cytoplasm, like is the case for MPTP, which makes it capable of producing complex I systemic inhibition (Brown, et al, 2006).

According to Brown et al, Rotenone infusion in rats reduces specific binding of complex 1 by 75%, for 20-30ml rotenone concentration as well as causing nigrostriatal dopaminergic lesions. This affects the striatal nerve endings more severely, which aids in the
development of motor and postural deficit characteristics associated with the Parkinson’s disease.

This occurrence was observed through a reproducible rotenone model by Cannon, et al (2009) which accurately replicated many aspects of the disorder on humans, which aimed to study the systematic inhibition of mitochondrial complex 1 by Rotenone pesticide administration.

The Mechanism of Paraquat Pesticide Toxicity

A systemic review carried out by Vaccari, El Dib, & de Camargo (2017) acknowledges that Paraquat (1, 1′-dimethyl-4, 4′-bipyridine) has a high structural similarity with the MPTP. Paraquat pesticides cause cellular toxicity by producing oxidative ROS oxides.

An experiment carried out on rodents’ further shows that the paraquat pesticide causes neuroinflammation, aggregation and the α-synuclein upregulation, which increases the risk of developing Parkinson’s disorder.

Paraquat pesticide reacts by undergoing a single electron reduction forming superoxide radicals. Unlike rotenone, the pesticide requires neutral amino acid transport system, which transports it to the brains striatal cells.

The penetration of paraquat pesticide into the brain is age dependent, with toxin penetration being higher in older adults (Berry, La Vecchia, & Nicotera, 2010).

Paraquat causes neural damage once in the brain resulting to Parkinson like syndromes. The similarity of Paraquat to MPTP/MPP+ is considered as proof that the penetration of paraquat pesticide into the human brain causes similar cytotoxic mechanism.

The Mechanism of Deldrin Pesticide Toxicity

Similarly, Dieldrin pesticide has several toxic effects in the mitochondria, such as increased ROS production and the mitochondria –mediated apoptosis stimulation, which is a pathogenic mechanism for Parkinson’s disease. The Pyrethroids pesticides increase the up of DATmediated dopamine, which causes neuro-toxity.

In addition, they induce an overload of NA+ which causes endoplasmic reticulum stress, induce cognitive impairments and striatal dopamine levels, which are neuropathological changes observed in Parkinson’s disease patients (Nasuti, et
al, 2017).

Heavy Metals as Environmental Toxins and Parkinson’s Disease Risk Factors

Heavy metals are environmental toxins that are also associated with high Parkinson disorder risk (Chin-Chan, Navarro-Yepes, & Quintanilla-Vega, 2015). According to Chin-Chan, Navarro-Yepes, & Quintanilla-Vega, heavy metal environmental toxins especially manganese disrupt metabolic pathways of the body.

The most vulnerable body system is the brain, as a result of its high glucose metabolism rate, low antioxidant levels and high polyunsaturated fatty acids levels. In addition, the brain has high enzymatic activities involving heavy metals such as manganese, which plays a significant role in cellular hemostasis.Other high risk heavy metals include iron and Lead.

Manganese Toxin Accumulation

Although there is no sufficient epidemiologic evidence to support the relationship between exposure to Manganese and increased risk of developing Parkinson’s disorder, several studies have associated Manganese heavy metals accumulation to neurological syndromes that exhibit similarities to Parkinson’s disease symptoms (Guilarte, 2013).

These sysmptoms include cognitive deficits and neuropsychological abnormalities, which have been reported by people with prolonged exposure to Manganese, such as welders and smelters. This provides evidence that excessive exposure to
manganese causes neurotoxicity.

Iron Toxin Accumulation

Iron has pro-oxidant properties that are assumed to have a role in Parkinson’s disorder pathogenesis (Zheng, & Monnot, 2012). The highest concentrations of iron in the human brain are found in the substantial
nigra of the brain. Iron accumulation increases the vulnerability to develop Parkinson’s disorders, as a result of iron reaction with ROS from dopamine metabolism. This has been observed in the postmortem brain analyses of patients with Parkinson’s disease.

Similar results are shared in a study carried out by
Kaur et al (2007), which found out that mice administered with iron showed signs of progressive neurodegeneration of the midbrain, increasing the vulnerability to the toxicity. This is an indication of the high risk of developing Parkinson’s due to excessive exposure to iron.

Zhang, (2012) also associated lead accumulation with Parkinson’s development. A prolonged exposure to lead heavy metals metal, for more than 20 years, plays a significant role in the development of Parkinson’s disorder symptoms. 

Treatment of Parkinson’s Disease

Major treatment approaches for Parkinson’s disease focuses extensively on the replacement of dopamine to reduce the severity of motor symptoms. Levodopa, which is a precursor to dopamine is used as a gold standard for dopamine replacing agent (Jankovic, & Aguilar, 2008). It works by temporarily stimulating and restoring the striatal dopaminergic
neurotransmissions. However, dopamine itself cannot cross the brain barrier, hence administering itself only is ineffective. Levodopa is distributed through the body to the brain as L-amino acid decarboxylase, which converts to dopamine after crossing the brain barrier (LeWitt, 2008). According to LeWitt, the drug is co-administered with other drugs to increase efficiency and reduce side effects. This include carbidopa or benserazide, which act as AAAD inhibitor. These drugs prevent the conversion of dopamine in the central nervous system, which
is associated with significant effects including “wearing off” and dyskinesia. The effects depend with the dose and duration of treatment. The drug is administered orally and can also be administered intravenously.

Other treatment options include the dopamine receptor agonists. These drugs work as a compensation for the hyperdopaminergic functions, by directly activating the central synaptic dopamine receptors within the caudate region of the brain, which results in balancing dopaminergic effects (DeMaagd, & Philip, 2015). Examples of these drugs include the ergot
class derivatives such as Bromocriptine which is although it’s mostly used in patients with neuroleptic malignant syndrome and hyperprolactinemia, it’s approved in the treatment of the Parkinson’s disease. Non ergot class examples for the dopamine agonists include the ropinorole
and pramipexule. These drugs are more efficient, and have improved safety and highly tolerable by the patients with the disorder (DeMaagd, & Philip, 2015). The major complications associated with their treatment include fibrotic complications, pulmonary infiltrates and effusions.

Interactions of Environmental Toxins and Genetics

The major process associated with Parkinson’s disease include mitochondrial dysfunction, the oxidative stress, inflammation, microglial activation, and nitrative stress. The processes are influenced with exposure to the environment. Gene-environment interplay contributes to monogenic forms of Parkinson’s disorder, with major mutations being on SNCA and LRRK2 genes (Polito, Greco, & Seripa, 2016). The mutation causes the peculiar features associated with the disorders dominant form. Several epidemiological studies have suggested a relationship between the exposure to environmental toxins and polymorphism in genes, which affects how these toxins are absorption, their metabolism
and excretion. For instance, genetic variants effects on p-glycoprotein, a gene that provided the brain against neurotoxins and an efflux transporter, increases the risk of developing the disorder.

Exposure to pesticides increases the gene polymorphism as compared to those nonexposed. Another example is on the polymorphism of paraoxanases and cytochromes P450, a class of enzymes involved in xenobiotic metabolism helping in detoxification of pesticide chemical, increases the risk of developing the disorder by 2-fold. Patients with a higher exposure to pesticides are at a higher risk of the gene polymorphism, which subsequently increases the risk of developing the disorder (Horowitz, & Greenamyre, 2010). Other examples is the  polymorphism of glutathione S-transferases (GST) M1, T1 and P1. People with two copies of the GSTT1 gene have a lower risk of developing Parkinson disorder. The dopamine transporter gene variability and exposure to pesticides such as Paraquat interact increasing the risk of developing the disorder. Mutations of SNCA and LRRK2 genes are highly associated with the high risk of the disorder as they affect the deregulation on various corresponding pathways for each gene, which plays an essential role Parkinson’s disease pathogenesis. Their mutation is also associated
with neudegeneration and neuronal loss.

Effects of Parkinson’s Illness as a Function of Toxin Exposure Time

The time of pesticide exposure increases the risk of Parkinson’s diseases. According to Hancock et al, (2008), there is a positive correlation between the exposures of pesticides with the development of the disorder. Early exposure to pesticides causes a disturbance in the gene expression, which causes damage to substantial nigra, with a combined odds ratio of 1.94, at 95% confidence interval (Freire, & Koifman, 2012). Several ways through which the pesticide maybe be absorbed include through inhalation, ingestion and through the skin for some pesticides types. Exposure time influences dopaminergic neurotransmission, which further increases the risk of development of the Parkinson’s disease.


All the pesticides and heavy metals associated with the high risk of Parkinson’s diseases have been quantified in the postmortem for patients with Parkinson’s disorder. In additional several epidemiological studies have also indicated a significant relationship between various
pesticides use by farmers with Parkinson’s disorder (Brown, Rumsby, Capleton, Rushton, & Levy, 2006). Existing Toxicological data at molecular level supports the epidemiological evidence available, which further associates pesticides and heavy metals with the Parkinson’s
disorders. Parkinson’s disorder has a significant impact on the normal functioning, with majority of the cases, accounting for 95% termed as sporadic. However, there is no definitive test for the condition, and diagnosis relies on the symptoms of the disease evaluated in a scale of 1-5.
Majority of the studies associate Parkinson’s disease to environmental toxins and heavy metals. The pesticides affect the mitochondria functions. Rotenone is a potent non-competitive mitochondria inhibitor which is derived from the leguminosa family plants, which alters mitochondria functions when exposed. The pesticide has a similar structure to the MPTP, making it a complex 1 systematic inhibitor. Other pesticides which also exposure increases the risk of developing Parkinson’s disorder include Dieldrin which induces cognitive impairments as observed in Parkinson’s patients. Exposure to pesticides is also associated with gene mutation,
which increases the risk for developing the disorder.

Majority of the literature which addresses the treatment of the condition is limited. There is a need for more research for the condition, especially that huge side effects which exist from the current treatment alternatives, making clinical treatment of the condition a challenge. Based on the research, there is need for more treatment options, to replace the decade’s old Levodopa, which is a precursor to dopamine is used as a gold standard for dopamine replacing agent. New government policies should be introduced to regulate the use of pesticides, which are associated with Parkinson’s diseases such as rotenone and Paraquat.

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