1 Apr, 2025
Detailed Study About Parkinson’s Disease
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Detailed Study About Parkinson’s Disease

Lipuna Kundu

M.Pharm 2nd semester,
Geeta Institute of Pharmacy, Geeta University

Introduction

Parkinson’s disease is also called movement disorder. This is mainly related to the nervous system. It causes the degeneration, weakening, and death of neuron cells in one part of the brain which leads to problems in movement, tremors, stiffness, and impaired balance. As symptoms increase people with Parkinson’s disease may have difficulty walking, talking, and completing other simple tasks.

It was 1st described by James Parkinson in 1817 and further characterized by Jane-Martin Charcot in the Mid-1800s. 1865 William Rutherford Sanders of Edinburgh coined the term “Parkinson’s disease”. In 1917 the anatomic substrate of Parkinson’s disease was identified. In the 1960s the discovery of dopaminergic defects and the mapping of dopamine’s synthetic pathway led to the initial human trials of levodopa.

Parkinson’s Disease (PD) ranks as the second most common neurodegenerative disease, trailing only Alzheimer’s Disease (AD). It’s prevalent in about 0.5–1% of individuals aged 65–69, and this figure climbs to 1–3% among those 80 and older. As the population ages, the prevalence and incidence of PD are projected to surge by over 30% by 2030. This increase will have significant direct and indirect impacts on society and the economy

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Clinical features: -

The clinical features of Parkinson’s disease are mainly associated with motor symptoms like tremor, rigidity, and bradykinesia with postural instability. It may also be associated with nonmotor symptoms, and these often precede the motor symptoms by years. The first symptoms of PD, that is the premotor or prodromal phase of the disease may start as early as 12 to 14 years before diagnosis. There is increasing evidence that the early disease process begins in the peripheral autonomic nervous system and/or the olfactory bulb followed by a sequence of neuropathological changes throughout the central nervous system starting in lower brainstem structures before the substantia nigra. Such a pathway can explain the early symptoms among PD patients, including hyposmia, constipation, and rapid eye movement sleep disorders often seen well before the motor symptoms manifest.

This prodromal state in PD has now become of increasing interest, because this may be an ideal time point for therapeutic intervention. Many trials investigating potential therapies include patients with early Parkinson’s disease, within 2 years of diagnosis even then, significant dopaminergic neuron loss will have already occurred.

Clinical diagnosis of PD depends on the presence of bradykinesia with either resting tremor or rigidity. Symptoms early in the course characteristically are asymmetric, without atypical features such as cerebellar signs, early significant autonomic dysfunction, supranuclear vertical gaze palsies, or cortical sensory impairment-which would point to a different diagnosis. Asymmetric symptom onset and a good response to levodopa are supportive of the diagnosis of PD and represent two of the most important features that distinguish PD from other forms of Parkinsonism.

The disease progresses with both motor and non-motor symptoms co-occurring. PD is a very heterogeneous disease, and attempts have been made to subclassify it further. One suggested classification, mainly based on clinical features, proposes two types: a tremor-dominant PD and a non-tremor-dominant PD. A patient with a tremor-dominant PD generally does not have other motor symptoms and generally responds better to dopamine replacement therapy.

In the initial stage of Parkinson’s disease, nonmotor symptoms are observed commonly which may increase and become more difficult to manage. Early nonmotor symptoms affect autonomic dysfunction, pain, olfactory ability, fatigue, sleeping problems, and cognitive and psychiatric disturbances. They highly affect the quality of life of the patient. Autonomic symptoms are difficult to treat; orthostatic hypotension creates the most problems for such patients. Urinary incontinence and constipation are common, and dementia occurs among 83% of the patients with PD in 20 years following a diagnosis. The contribution of these non-motor symptoms is huge in causing disability and poor quality of life.

Etiology: -

The risk factor of PD is related to both genetic and environmental factors. Age is the biggest risk factor for PD. The etiology of PD has evolved significantly over the last century. In 1919, it was first recognized that one characteristic feature in the post-mortem examination of the brain in PD is loss of pigmentation in the substantia nigra of the midbrain. It has been further understood since the 1950s that the pigmented neurons which are lost within the substantia nigra are dopaminergic and it is the loss of dopamine within subcortical motor circuitry implicated in the mechanism of the movement disorder of PD.

Parkinson’s disease (PD) is a disorder that mainly affects a part of the brain called the basal ganglia, which is responsible for controlling movement. The striatum, an important part of the basal ganglia, receives signals from different areas of the cortex that can either stimulate or inhibit activity. In PD, there is a gradual loss of dopamine-producing neurons, especially in the substantia nigra, which is a specific region within the basal ganglia. This decrease in dopamine disrupts the normal functioning of the neural circuits in the basal ganglia, resulting in the typical motor symptoms associated with Parkinson’s disease, including tremors, stiffness, and slowness of movement.

The use of pesticides, herbicides, and proximity to industries has been suggested as a cause of PD. Parkinsonian features similar but not identical to the disorder were produced in humans following the injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. This chemical accumulates in the mitochondria. It is also suggested that the etiology of the damage to the thalamic nuclei is linked to oxidation and production of free radicals.

Genes are important in that the risk of PD the siblings are more vulnerable to pd if any person of the family is affected by this disease. This also tends to happen much earlier in life. SNCA: Mutations lead to abnormal protein accumulation (Lewy bodies). LRRK2: Commonly mutated, especially in certain populations, linked to both familial and sporadic PD. PARK2, PINK1, DJ-1: Mutations in these genes cause early-onset PD, affecting protein degradation, mitochondrial function, and oxidative stress response. GBA: Mutations raise PD risk by disrupting cellular waste processing.

Deposition of more amount of alpha-synuclein is a major factor for Lewy bodies and is present at autopsy. Research indicates that alterations in the function of this protein may significantly contribute to the disease’s onset. By concentrating on this relationship, we have the potential to discover new treatments and offer renewed hope to PD patients.

PD also affects more men than women

Diagnosis: -

Currently, there is no specific test to definitively diagnose Parkinson’s disease. Instead, a diagnosis is made by a neurologist, a doctor who specializes in nervous system conditions, based on the patient’s medical history, a review of symptoms, and a thorough neurological and physical exam.

Diagnosing Parkinson’s disease can take time. The doctor may ask for regular consultation with a trained neurologist in movement disorders to monitor symptoms and evaluate the condition over time.

Several tests and procedures may be used during the diagnostic process:

Physical and neurological exam: This involves taking the patient’s medical history and performing a neurological exam that assesses thinking abilities, senses, coordination, and reflexes.

Blood and lab tests: These tests are conducted to find out other conditions that may show similar symptoms.

Imaging tests: MRI, brain ultrasound, and PET scans can help exclude other potential causes of the symptoms but are not particularly useful in diagnosing Parkinson’s disease itself.

Dopamine transporter (DAT) scan: This specialized scan (a type of SPECT scan) can help support a Parkinson’s diagnosis and differentiate between different types of tremors. However, the diagnosis is primarily based on symptoms and the neurological exam, and most people don’t need a DAT scan.

Genetic testing: This may be used to check for genetic mutations if there is a family history of Parkinson’s or if the patient has early-onset disease.

Medicinal trial: Sometimes, patients may be given Parkinson’s medications to see if their symptoms improve. If the patient responds well, this can help confirm the diagnosis. The medicine must be given at a sufficient dose to see the effect, as small doses for a short period aren’t reliable.

Follow-up appointments: Regular check-ins with movement disorder neurologists over time may be necessary to confirm a diagnosis.

Alpha-synuclein test: This newer test, also known as the alpha-synuclein seed amplification assay, can detect Parkinson’s disease before symptoms appear. Alpha-synuclein is a protein that forms clumps in the brain, a hallmark of Parkinson’s. The test is performed on spinal fluid or skin samples.

This large study marked a significant step toward improved Parkinson’s diagnosis, research, and treatment trials. However, larger studies are needed for further validation. There is hope that future tests could be performed using blood samples instead of spinal fluid.

Treatment: -

Parkinson’s disease is incurable but there are some medicines that are used to control the disease condition. When medicines are not working some people may have surgery. The doctor may recommend aerobic exercise, and physical therapy and focuses on balance and stretching and speech therapy.

Medicines: -

Medicine may help to treat problems related to walking, movement, and tremors. Medicine works by increasing or substituting dopamine in the brain, in patient, the dopamine level mainly remains low but we can not give dopamine directly because they cannot cross the blood-brain barrier so their prodrugs are used.

Levodopa-Carbidopa (Sinemet, Rytary): The most effective treatment, levodopa converts to dopamine in the brain, while carbidopa helps reduce side effects like nausea. Common issues include nausea, lightheadedness, and dyskinesia (involuntary movements). Over time, its effects may wear off. There are also inhaled (Inbrija) and infused forms (Duopa).

Dopamine Agonists (Pramipexole, Rotigotine, Apomorphine): This mimics dopamine but can cause side effects like nausea, hallucinations, and compulsive behaviors.

MAO-B Inhibitors (Selegiline, Rasagiline): These prevent dopamine breakdown, extending levodopa’s effectiveness, but may cause insomnia, confusion, and hallucinations.

COMT Inhibitors (Entacapone, Opicapone): Help prolong levodopa’s effects but may cause nausea and involuntary movements.

Anticholinergics (Benztropine): Used for severe tremors, but less common due to side effects like memory loss and confusion.

Amantadine: Helps control involuntary movements in advanced Parkinson’s but may cause cognitive issues and swelling.

Pimavanserin (Nuplazid): Treats hallucinations and delusions associated with Parkinson’s disease, specifically targeting psychosis without affecting dopamine levels.

Adenosine Receptor Antagonists (e.g., Istradefylline): Help prevent dopamine “wearing off” in Parkinson’s patients, allowing for more consistent dopamine release to manage motor symptoms.

Surgery: -

Deep brain stimulation surgery is done to treat Parkinson’s disease. It involves inserting electrodes in the brain which is connected to a generator (pacemaker-like device) which inserted under the skin of the chest near the collarbone. The generator sends an electrical signal to the brain that reduces symptoms

It needs a routine check-up to adjust the settings of the device. some people may experience complications due to stimulation. DBS helps improve severe tremors and control involuntary muscle movements, and effective in controlling changing responses to levodopa which can’t be improved by medicines. DBS may have prolonged activity to control symptoms but does not keep Parkinson’s disease from getting worse.

Side effects of surgery

  • Bleeding in the brain.
  • Injury or death of tissue.
  •  
  • Skin breakage.
  • Muscle twitches.
  •  
  • Speech or vision problems.

Lifestyle changes and complementary and supportive therapies: –

A wide variety of complementary and supportive therapies and lifestyle changes may be used for PD, including

A healthy diet can support overall well-being for people with Parkinson’s disease (PD), with fiber-rich foods and plenty of fluids helping to alleviate constipation. However, a high-protein diet may interfere with levodopa absorption.

 

Exercise, including walking, yoga, cycling, and swimming, can improve mobility, balance, and strength in PD patients. Ongoing research is exploring whether high-intensity exercise might slow PD progression. Always consult a doctor before starting a new exercise routine.

Herbal medications: -

Brahmi or Bacopa monniera: The medical plant Bacopa monnieri (Bm) has anti-oxidant, anti-inflammatory, anti-microbial, neuroprotective, and memory-boosting qualities.  In both transgenic and toxin-induced animal models, Bm extract (BME) has demonstrated promise in improving cognitive abilities and exhibiting anti-parkinsonian properties.  Research shows that BME shields mice, Drosophila, and C. elegans models of Parkinson’s disease (PD) from oxidative damage brought on by toxins like paraquat and rotenone.

By restoring electron transport chain activity and preserving mitochondrial membrane potential, BME supplementation improves mitochondrial function, lowers oxidative indicators, and increases antioxidative enzyme activity.  Furthermore, it improves locomotor and cognitive abilities in PD models via controlling tyrosine hydroxylase activity and neurogenic gene expression.  Despite its potential as a natural medication to treat Parkinson’s disease, further research is required to comprehend how it works completely.

Ashwagandha or Withania somnifera (Ws): it is a traditional Indian medicinal plant that has anti-inflammatory, antioxidant, neuroprotective, and memory-boosting qualities.  Research shows that Ws root extract improves dopamine levels and motor skills in mice and rat models of Parkinson’s disease (PD), lowers oxidative stress, and raises glutathione levels.  Additionally, it improves mitochondrial function and increases the production of tyrosine hydroxylase.

Ws exhibits promise in mammalian models, however, research in the Drosophila PD model has produced conflicting findings.  Furthermore, in toxin-induced PD models, Ws suppresses Bax and increases Bcl-2 expression, which helps control apoptosis.  Even though it has the potential to be a neuroprotective agent, more investigation is required to confirm its effectiveness and elucidate its mode of action in the treatment of Parkinson’s disease.

Turmeric or Curcuma longa: Turmeric, also known as Curcuma longa (Cl), is a medicinal herb that has antibacterial, anti-inflammatory, bioprotective, and antioxidant qualities.  Its main bioactive ingredient, curcumin, has demonstrated potential in treating neurological conditions including Parkinson’s disease (PD).  According to studies, curcumin preserves mitochondrial activity in PD models, increases striatal dopamine levels, and guards against oxidative stress.  Additionally, it increases the activity of antioxidant enzymes, lowers nitrosative stress, and promotes memory and motor skills.

Pre-treatment with curcumin decreases apoptosis and increases ATP synthesis and mitochondrial respiration.  Curcumin-glucoside, a synthetic derivative, also inhibits α-synuclein fibrillization, which is essential for the advancement of Parkinson’s disease.  Crucially, curcumin is a potent option for PD treatment because it shows no signs of toxicity.  Its therapeutic promise has to be confirmed by additional clinical research.

Ginkgo Biloba: The benefits of Ginkgo biloba (Gb) include neuroprotection, anti-aging, anti-inflammatory, and antioxidant effects.  In models of Parkinson’s disease (PD), its extract, EGb 761, has demonstrated neuroprotective effects by lowering behavioral impairments, boosting muscular coordination, and improving locomotor activity.  In rat models of Parkinson’s disease, Gb therapy lowers oxidative stress and apoptosis, raises dopamine levels and upregulates antioxidant enzymes (GSH, SOD, and Catalase).

Furthermore, EGb 761 enhances mitochondrial activity, stabilizes the redox state, and guards against levodopa-induced toxicity, indicating the possibility of a combined therapy.  Gb seems potential for treating Parkinson’s disease (PD) because it can pass the blood-brain barrier, but more clinical trials are required to confirm its effectiveness.

Conclusion: -

A progressive neurodegenerative condition that impacts both motor and non-motor abilities is Parkinson’s disease (PD). Levodopa-Carbidopa, dopamine agonists, MAO-B inhibitors, and deep brain stimulation are examples of conventional treatments that assist control symptoms but do not stop the disease’s progression.  Herbal remedies with neuroprotective properties include Bacopa monnieri, Withania somnifera, Curcuma longa, and Ginkgo biloba.  They boost mitochondrial function, lower oxidative stress, raise dopamine levels, and control apoptosis.  While Ginkgo Biloba (EGb 761) enhances locomotor activity and guards against levodopa toxicity, Curcuma longa inhibits α-synuclein fibrillization.  To confirm their effectiveness and maybe supplement traditional PD treatments, more clinical trials are required.

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