What is Parkinson’s Disease (PD)?

Parkinson’s disease (PD) is a progressive neurological disorder that primarily affects movement. It is characterized by a gradual loss of nerve cells in the brain that produce dopamine, a neurotransmitter involved in coordinating movement and regulating mood.


The exact cause of Parkinson’s disease is not fully understood, but it is believed to result from a combination of genetic and environmental factors. Some potential contributors to the development of PD include:


  • Genetic Mutations: Certain genetic mutations have been associated with an increased risk of Parkinson’s disease. However, these mutations are relatively rare and account for only a small percentage of cases.


  • Environmental Factors: Exposure to certain environmental toxins or chemicals, such as pesticides or herbicides, may increase the risk of developing Parkinson’s disease. Additionally, head injuries or trauma may also be linked to an increased risk of PD.


  • Age: Parkinson’s disease is more common in older adults, with the majority of cases diagnosed in people over the age of 60. However, it can also occur in younger individuals, although less frequently.


  • Gender: Men are slightly more likely to develop Parkinson’s disease than women, although the reasons for this gender difference are not well understood.


  • Neurodegeneration: Parkinson’s disease is characterized by the progressive degeneration of nerve cells (neurons) in the substantia nigra region of the brain. These neurons are responsible for producing dopamine, a neurotransmitter that helps regulate movement and coordination. As dopamine levels decrease, individuals with PD experience symptoms such as tremors, rigidity, slowness of movement (bradykinesia), and difficulties with balance and coordination.


What is the relationship between PD and oxidative stress?

The relationship between Parkinson’s disease (PD) and oxidative stress is a significant area of research and is thought to play a crucial role in the development and progression of the condition. Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them with antioxidants, leading to damage to cellular structures such as proteins, lipids, and DNA. In the context of Parkinson’s disease, several key factors contribute to oxidative stress:


  • Dopaminergic Neuron Vulnerability: Dopaminergic neurons in the substantia nigra region of the brain, which are primarily affected in Parkinson’s disease, are particularly vulnerable to oxidative stress. Dopamine metabolism itself generates ROS as a byproduct, and the high metabolic rate of these neurons makes them susceptible to oxidative damage.


  • Mitochondrial Dysfunction: Mitochondrial dysfunction is a hallmark feature of Parkinson’s disease, and impaired mitochondrial function leads to increased production of ROS. Mitochondria are the primary cellular organelles responsible for generating energy in the form of adenosine triphosphate (ATP), and dysfunctional mitochondria can disrupt cellular energy metabolism and increase oxidative stress.


  • Alpha-Synuclein Aggregation: Aggregation of alpha-synuclein protein into toxic clumps, known as Lewy bodies, is a pathological hallmark of Parkinson’s disease. Alpha-synuclein aggregates can induce oxidative stress and impair cellular function by interfering with mitochondrial function, disrupting protein degradation pathways, and promoting inflammation.


  • Inflammatory Response: Chronic inflammation in the brain, driven in part by the presence of alpha-synuclein aggregates and activated microglia, contributes to oxidative stress in Parkinson’s disease. Inflammatory cytokines and reactive oxygen species released by activated immune cells further exacerbate neuronal damage and promote neurodegeneration.


  • Environmental Toxins: Exposure to environmental toxins and pesticides, such as rotenone and paraquat, has been implicated in the development of Parkinson’s disease and can induce oxidative stress in dopaminergic neurons. These toxins interfere with mitochondrial function and increase ROS production, leading to neuronal damage and cell death.


  • Impaired Antioxidant Defenses: Parkinson’s disease is associated with deficits in antioxidant defense mechanisms, including reduced levels of endogenous antioxidants such as glutathione and impaired activity of antioxidant enzymes such as superoxide dismutase and catalase. This imbalance between ROS production and antioxidant defenses contributes to oxidative stress and exacerbates neuronal damage in PD.


Overall, oxidative stress is considered a key pathological mechanism underlying the neurodegeneration observed in Parkinson’s disease. Strategies aimed at reducing oxidative stress, such as antioxidant therapy or targeting pathways involved in ROS production and mitochondrial dysfunction, represent potential therapeutic approaches for slowing the progression of Parkinson’s disease and protecting dopaminergic neurons from oxidative damage.