Parkinson’s Disease Explained: From Early Symptoms to Latest Research

What is Parkinson’s disease?

Parkinson’s disease is a progressive neurodegenerative disorder that primarily impacts the nerve cells (neurons) in the brain responsible for producing dopamine — a chemical in the brain that helps regulate movement and coordination. The progressive loss of these nerve cells results in people experiencing symptoms such as uncontrolled movements, shaking, stiffness, and problems with balance and coordination. ^{1, 2}

The number of people diagnosed with Parkinson’s disease has been rising since the 1980s, with a faster increase in the last 20 years. This increase is partly attributed to an aging population worldwide, as Parkinson’s tends to affect older adults more frequently. ³ Currently, it is estimated that 10 million people worldwide are living with the condition, including approximately 1 million in the United States. ^{4, 5}

What causes Parkinson’s Disease?

The exact cause of Parkinson’s disease is still not fully understood, but research suggests that several biological processes contribute to its development:

• Alpha-synuclein (α-Synuclein): α-Synuclein is a protein naturally found in the brain that is believed to help nerve cells communicate. In Parkinson’s disease, α-synuclein proteins frequently clump together to form structures called Lewy bodies. As these clumps build up, they can interfere with brain function and cause neuron loss. ^{1, 6, 7, 8, 9}
• Oxidative stress: As part of normal cell function, the body produces toxic byproducts known as reactive oxygen species. In Parkinson’s disease, too many of these toxic byproducts are produced while the body’s ability to eliminate them declines. This imbalance leads to their accumulation, a process known as oxidative stress, which damages cellular components and contributes to neuron loss. ^{7, 8, 10}
• Mitochondrial dysfunction: Mitochondria are tiny structures in cells that produce energy. They become damaged in Parkinson’s disease, which leads to reduced energy availability and an increased production of toxic byproducts, such as reactive oxygen species. These byproducts may harm brain cells and are thought to contribute to the development of Parkinson’s disease. ^{7, 8, 11}
• Neuroinflammation: Parkinson’s disease is associated with an overactive immune response in the brain, leading to chronic inflammation that damages neurons and accelerates disease progression. ^{7, 10}
• Iron buildup: In certain cases of Parkinson’s disease, iron can accumulate in specific regions of the brain. The excess iron may damage mitochondria, leading to the production of toxic reactive oxygen species and oxidative stress, which can harm neurons. Additionally, iron can also contribute to the aggregation of proteins such as α-Synuclein or disrupt several cellular processes, further contributing to neuronal damage. ^{8, 12}

Risk Factors for Parkinson’s disease

Several factors can increase the risk of developing Parkinson’s disease. Aging is the most important risk factor, as the likelihood of developing Parkinson’s increases significantly after age 60 and rises exponentially in later decades. ¹³ Additionally, men are 1.5 to 2 times more likely to develop Parkinson’s disease than women. ^{1, 14, 15} A family history of Parkinson’s can further increase risk. Environmental factors, such as exposure to pesticides, have also been linked to a higher risk of developing the disease. Research suggest that some pesticides could damage neurons, suggesting that contact with these chemicals may contribute to the disease’s onset. ^{1, 13, 16}

Most cases of Parkinson’s disease (about 90%) are sporadic, meaning they occur randomly without a clear genetic link. However, approximately 10% of cases have a genetic basis. ^{13, 17} Scientists have identified mutations in more than 20 genes associated with Parkinson’s disease, though some have stronger evidence of being involved in the disease than others. ¹⁸ Some of the genes that through research have been clearly linked to the disease include:

– SNCA and LRRK2: These genes are involved in the production and processing of α-synuclein. Mutations in these genes could lead to an increase in a-synuclein aggregation, potentially contributing to the development of Parkinson’s disease ^{1, 8, 9}

– PRKN, DJ-1, and PINK1: These genes help regulate mitochondrial function and manage oxidative stress. Mutations in these genes could lead to the accumulation of toxic byproducts such as reactive oxygen species, making neurons more vulnerable to damage and accelerating disease progression. ^{1, 8}

– GBA: This gene helps break down fatty substances in cells. Mutations in GBA can lead to a buildup of a fatty substance called glucocerebroside in brain cells, a process that has been linked to a higher risk of developing Parkinson’s disease. ^{1, 19}

What are the symptoms of Parkinson’s disease?

Parkinson’s disease affects each person differently, with symptoms developing gradually and often starting on one side of the body before affecting both. The most common symptoms of Parkinson’s disease are:^{1, 20}

• Tremor (shaking): This usually starts in a hand, but it can also start in the foot or the jaw. It is characterized by a rhythmic back-and-forth motion that often leads to a rhythmic rubbing of the thumb and forefinger, a movement known as the “pill-rolling” tremor. ¹
• Rigidity (muscle stiffness): The muscles remain tense and tight, leading to discomfort or pain. When someone tries to move the affected arm or leg, the limb may move in a jerky, ratchet-like motion, known as “cogwheel” rigidity. ¹
• Bradykinesia (slow movement): Movements become slower and less automatic, making daily tasks like buttoning a shirt, walking, or eating take longer. It can also affect facial expressions, leading to a less animated appearance known as “masked face.” ¹
• Postural instability: It refers to the difficulty of maintaining balance due to the loss of postural reflexes — automatic responses that help the body stay stable while standing or moving. This can affect the ability to adjust to balance shifts, maintain an upright posture, and rotate the trunk, increasing the risk of falls. ^{1, 20}

Other possible symptoms can include difficulty swallowing and chewing, speech impairments, sleep disturbances, urinary problems, constipation, muscle cramps, fatigue and mental health problems such as depression or anxiety. ¹

Diagnosis of Parkinson’s disease

There is no specific test to diagnose Parkinson’s disease. Instead, physicians rely on a combination of medical history, neurological examinations, and specialized tests to confirm the diagnosis and rule out other conditions.

A physical and neurological examination is usually the first step, where physicians assess cognitive abilities, coordination, reflexes, and sensory function to check for signs of Parkinson’s.^{1, 21}

Brain imaging can also help to rule out other conditions that may cause symptoms similar to Parkinson’s disease. These imaging techniques may include:

• Magnetic resonance imaging (MRI): It produces detailed brain images using radio waves and a strong magnetic field. ^{1, 21}
• Single-photon emission computed tomography (SPECT): This technique involves using a radioactive substance and a specialized camera to generate 3D pictures of the brain.^{1, 21, 22}
• Dopamine Active Transporter Scan (DATscan): In some cases, this approach may be used to measure dopamine levels in the brain. However, it cannot distinguish Parkinson’s from other disorders that also involve dopamine loss. ^{1, 21, 22}

In certain cases, genetic testing may be recommended to identify mutations linked to inherited forms of Parkinson’s. ^{1, 21} Additionally, blood and laboratory tests can help rule out other medical conditions that might be causing the symptoms. ^{1, 21}

Treatment for Parkinson’s disease

Currently, there is no cure for Parkinson’s disease. However, various therapies, including medications and surgical options, can help manage symptoms and improve quality of life. ¹

Medications

Most medications prescribed to treat Parkinson’s work by increasing dopamine levels in the brain or mimicking dopamine’s effects. Over time, some medications may become less effective (“wearing-off phenomenon”), which is why doctors may adjust treatments as the disease progresses. ¹⁹ They include:

• Dopamine precursors: Substances like levodopa that convert into dopamine once they arrive to the brain. Levodopa is always combined with other drugs, such as carbidopa, to prevent it from breaking down before reaching the brain. ^{1, 19}
• Dopamine agonists: These drugs are not dopamine themselves but mimic its effects in the brain. Common dopamine agonists include pramipexole and ropinirole ^{1, 19}
• Dopamine breakdown inhibitors: These medications help prevent the existing dopamine from breaking down, so its effects last longer. It includes medications such as selegiline or entacapone. ^{1, 19}

Other drugs used to manage Parkinson’s tackle other mechanisms. Among them, anticholinergics can help to control tremors by blocking or reducing the effects of acetylcholine, another brain chemical involved in movement, while amantadine is sometimes used to reduce involuntary movements (dyskinesia). ^{1, 19}

For a list of these medicines, including their current drug authority approval status, please see Table 1.

Surgery

Surgery may be an option for individuals with Parkinson’s disease when medications are no longer effective in controlling symptoms: ¹

Lesion surgery: This procedure selectively destroys small areas of the brain associated with Parkinson’s disease symptoms. While it can help in some cases, it permanently damages brain tissue. If the procedure causes side effects or does not help, there’s no way to reverse it.  This technique has mostly been replaced by Deep Brain Stimulation (DBS). ¹

Deep brain stimulation (DBS): It involves implanting an electrode in the brain, connected to a pulse generator placed under the collarbone. The device delivers controlled, painless electrical signals to the brain that can help improve motor function. ^{1, 23}

Lifestyle and supportive therapies

In addition to medication and surgery, physical activity — such as walking, yoga, cycling, and swimming —can help improve mobility, balance, and strength. Vocal exercises may also improve speech and swallowing in some cases. People with Parkinson’s disease should always consult their physicians before starting these therapies. ¹ 

Investigational treatments

Different types of investigational treatments are being studied in Parkinson’s clinical trials to explore their potential to slow or prevent disease progression: ²⁴

Disease-Modifying Therapies (DMTs)

These therapies aim to slow or stop neuron loss by targeting key biological processes involved in the progression of Parkinson’s disease. Some of the treatments under investigation include:

• α-synuclein targeting therapy: Focuses on developing treatments that can break down toxic α-synuclein clumps. One approach involves modifying antibodies – proteins made by the immune system to fight infections – so they can specifically target and eliminate these clumps. ¹⁹
• GBA enhancers: Genetic changes that reduce the activity of the GBA gene are associated with α-synuclein buildup. Drugs like ambroxol, a common cough medicine, are being investigated for their potential to increase GBA activity and prevent α-synuclein accumulation. ¹⁹
• Anti-oxidative stress drugs: Scientists are studying treatments aimed at reducing oxidative stress, such as iron chelators to prevent toxic iron buildup and antioxidants (like coenzyme Q10) to help protect neurons. ¹⁹
• Anti-inflammatory drugs: Inflammation in the brain may contribute to Parkinson’s disease. Common drugs like ibuprofen, immunosuppressants, and statins may help reduce inflammation and protect brain cells. ¹⁹
• Mitochondria-boosting treatments: Researchers are investigating treatments to restore the function of mitochondria, the brain’s energy producers, which does not work properly in some cases of Parkinson’s disease. ¹⁹

Gene therapy for Parkinson’s disease

Gene therapy is an experimental treatment aimed to deliver specific genes into brain cells to help improve symptoms and protect neurons.^{9, 25} Various gene therapies are being studied in clinical trials for Parkinson’s disease, targeting different genes and biological processes:

• Dopamine-boosting therapy: It aims to deliver genes that help healthy brain cells produce more dopamine to compensate for the loss caused by Parkinson’s disease. ^{9, 25, 26}
• Neuroprotective gene therapy: This approach involves delivering protective genes, such as Glial cell line-derived neurotrophic factor (GDNF), which produces a protein that helps protect and support dopamine-producing neurons. ^{9, 25, 26}
• Rebalancing brain activity: This method focuses on introducing genes that produce chemicals to calm brain regions associated with movement issues.²⁵
• Gene therapy for specific genetic mutations: Some forms of Parkinson’s are associated with specific genetic mutations. This therapy focuses on delivering genes that correct or counteract the effects of these mutations. ²⁶

Stem cell therapy

Stem cells are special cells in the body that have unique abilities, such as, under certain circumstances, the capacity to transform into different types of cells, like muscle or brain cells. In the field of Parkinson’s disease, stem cell therapy is being studied to determine whether it can help to:

• Replace lost neurons: Researchers are exploring whether stem cells could develop into dopamine-producing neurons, replacing those destroyed by the disease. ²⁵
• Release protective substances: Some stem cells might release protective proteins, such as GDNF, which could help create a healthier environment for brain cells and support their survival. ²⁵

Conclusions

Parkinson’s disease (PD) is a neurological disorder that affects dopamine-producing neurons, leading to progressive difficulties with movement, balance, and coordination. While there is no cure, various treatments can help manage symptoms and improve quality of life. Some common Parkinson’s approved medications include dopamine precursors like levodopa, dopamine agonists such as pramipexole, and dopamine breakdown inhibitors such as selegiline or entacapone. Other drugs, such as anticholinergics and amantadine, may also be prescribed. In some cases, surgical options like lesion surgery or Deep Brain Stimulation (DBS) may be considered. There are several investigational treatments for Parkinson’s disease currently being studied in clinical trials, including disease-modifying therapies, gene therapy, and stem cell therapy.

Table 1. Medicines Approved by the FDA and EMA as of February 18th, 2025

To the best of our knowledge, the following medications have been approved by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of Parkinson’s disease. Note that some medications are marketed under different brand names in various regions.

*Numient (Levodopa/Carbidopa extended release) was approved in 2015 by the European Medicines Agency (EMA). However, the company that made Numient requested to withdraw its approval, so it is no longer available. ^{27, 28}

**Kynmobi (apomorphine hydrochloride) was approved in 2020. However, due to limited use, the company decided to stop selling it in the U.S. and Canada, and it is no longer available as of 2023. ²⁹

***Artane (trihexyphenidyl) is approved for use only in some European countries. Its availability depends on each country’s health regulations

Sources: 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45

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