Introduction Parkinsons Disease Definition Biology Essay

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Parkinsons disease is a chronic, progressive neurodegenerative disorder of muscle movement, affecting more than 350,000 Americans. The effects of the disease are characterized by prolonged disability and steadily worsening symptoms, although it is not generally in itself fatal.


Parkinson's disease is the second most common neurodegenerative condition after Alzhiemers disease [5]. Estimates of total prevalence vary widely, but approximately 50,000 people are diagnosed each year, and between 350,000 and 1,000,000 people suffer from the disease at any given time [2, 4]. Parkinson's is primarily a disease of the aged-the average onset age is 60 years, with only 5-10% of reported cases occurring in persons under 40. It is estimated that 1.6% of persons over the age of 65 and 2.4% of persons aged 80 to 89 have some form of the disease [3_5]. Because of the population over the age of 65 is expected to double by 2040, with a larger portion of those surviving beyond 85, thus the overall prevalence of Parkinson's disease is expected to increase as well [3, 5, 6].

Symptoms of Parkinsonism

The symptoms appear when 80% of the dopaminergic neurons are lost, demonstrating that the degenerative process is active for long time before the patients become aware of the disease. The rate of deterioration of these dopaminergic neurons are rapid in the early phase, with a decline of approximately 8-10 United Parkinson Disease Rating Scale (UPDRS) points in the first year [12,13]. Parkinsonism is a general term for the set of symptoms associated with Parkinson's disease [2]. The four major symptoms of Parkinsonism are tremor, rigidity, bradykinesia, postural instability.

Parkinsonian tremor is a resting tremor, which becomes more obvious and severe when the person is resting and improves with intentional movement [1, 2]. Tremor tends to be present in the hands, arms, legs, jaw and face [1]. Facial tremor usually involves the jaw, tongue and facial muscles, and not the shaking of the head seen in essential tremor [2]. Tremor in the hand is typically of the "pill rolling" type, where the thumb and forefingers seem to rotate about some point. Parkinsonian tremor is generally of fairly low frequency, ranging from 2.5 to 5 Hz [1] and is activated or increased by stress or emotional excitement. Tremor is typically not present while sleeping [2].

Rigidity is a stiff and weak feeling in the limbs and trunk. Rigidity can manifest as either a steady "lead pipe" resistance to movement, which occurs when a person's muscles remain tense and contracted, or as a "cogwheel effect", where resistance to movement occurs in short, jerky steps. This is caused by the lack of synchronization between antagonistic muscle pairs [1].

Bradykinesia is a general slowing of movement, sometimes coupled with an inability to initiate movement or akinesia. In advanced Parkinson's bradykinesia is subject to rapid fluctuations from ease of movement to inability to move, especially as medication doses wear off [2].

People with Parkinson's suffer from postural instability, in the form of impaired balance and coordination. This also manifests as a stooped and droopy posture, as well as halts and freezes while walking [1]. They also have a tendency to lean backwards or take short backward steps when bumped or starting to walk, an effect called "retropulsion". People with advanced Parkinson's tend to walk with short, rapid steps, which is called "festination" [2].


the pathogenesis of PD remains obscure. Many factors may play roles in PD, [6] these factors are genetic, infectious and immunological abnormalities, the effects of ageing, toxins (endogenous as well as exogenous), mitochondrial dysfunction, free radicals It also appears that free radicals may be one of the important agents responsible for destruction of SNpc neurons, thereby leading to PD., reactive oxygen species (ROS) which play role in oxidative stress (OX) of dopaminergic neurons of SNpc leading to neurodegeneration in PD[15, 16], and other environmental factors [7]. Reactive oxygen species (ROS) are generated during both enzymatic and non-enzymatic (autoxidation) metabolism of dopamine.


Diagnosis of Parkinson's disease is made clinically based on the person's history

and symptoms. There is no definitive laboratory test for Parkinson's disease. MR and CAT scans do not reveal Parkinson's, but can be useful in eliminating alternate diagnosis, such as cerebrovascular disease (stroke) [2], which may present similar symptoms. Radiological imaging devices such as PET and SPECT may reveal Parkinson's, but cannot necessarily differentiate Parkinson's from other neurodegenerative conditions. In addition, the cost and complexity of these devices tends to limit them to research facilities [7]. Protein aggregates called Lewy bodies are found in the brain tissue in Parkinsonian patients. Unfortunately, these can only be seen in autopsy. Such structures are also found in other diseases such as Multiple Systems Atrophy (MSA) and Pick's disease.


The major problem concerning a better therapeutic approach to the treatment and prevention of the PD is the enigma of its underlying cause. This has remained obscure in spite of many approaches and efforts made so far [2, 14]. The biological cause of Parkinson's disease is the death of neural cells in a part of the brain called the substantia nigra. This portion of the brain produces a neuro-transmitter called dopamine, which is essentially the medium by which signals are passed between neurons. The substantia nigra is the primary dopamine source for the corpus striatum, which helps regulate movement throughout the body. As the disease progresses and less dopamine is delivered to the corpus striatum outgoing signals become unreliable and movements become erratic and uncontrolled. The primary medication used to treat Parkinson's disease is levodopa. Dopamine itself is not effective as a medication because it cannot cross the blood-brian barrier, but levodopa is a dopamine precursor that can do so. It is then metabolized into dopamine by the enzyme dopa decarboxylase [2] in the substantia nigra. Because this enzyme is found throughout the body, very large doses of levodopa would be required to be effective. To counter this, dopa decarboxylase inhibitors (DDI's) such as carbidopa or benserazide are given with the levodopa dose. These are "peripheral" DDI's, in that they inhibit the metabolization of levodopa in the bloodstream, but do not affect metabolization in the brain. In the United States, the most common medication is sinemet, a carbidopa/Levodopa formulation available in various dossages and proportions. As the disease progresses and neurons in the substantia nigra die, the brain's capacity to metabolize Levodopa decreases and the medication dose must be increased. This is not a tolerance or loss of potency of the medication, but an effect of advancing degeneration [1] [2].

These medications can have unwanted side effects. The most noticeable side effect of levodopa is dyskinesia, or uncontrolled, swaying movements. Large, dance like movements called choreiform dyskinesias are seen in advanced patients. These movements typically occur at the peak of a leveodopa dose, although they also occasionally occur at the beginning and end of a medication cycle [1, 2]. Other side effects can include vivid dreams and nightmares, paranoia, and walking hallucinations. Occasionally these are severe enough to require institutionalization, especially in patients with reduced mental capacity or severe dementia [2].


The goal of neuroprotection is to limit neuronal dysfunction after injury and attempt to maintain the possible integrity of cellular interactions in the brain resulting in undisturbed neural function. Various kind of neuroprotectors classified as free radical scavengers, iron-chelators, anti-excitotoxic agents, apoptosis inhibitors, neurotrophic factors etc [19].

Body Self Defense against Parkinson Disease (PD)

Human body in general has evolved several defense mechanisms to counteract OS against some potentially toxic products such as vitamin E, vitamin C, vitamin A, glutathione and various antioxidant enzymes, but the brain appears to be more susceptible to this damage than other organs because of its low antioxidant capacity. The changes in the antioxidant defenses also support the evidence of OS in the substantia nigra what cause PD [17]. The most significant alteration is the decrease in the level of reduced glutathione (GSH). The cause of this reduction of GSH in PD patients is still unknown but it may be related to alteration in its synthesis, utilization or degradation [18].

Natural products

These days, the interest on natural products, especially herbal bioflavanoids, for the treatment of PD has been growing [20]. It has been documented that, many medicinal plants and their bioactive compounds including polyphenols exerts neuroprotective effects in Alzheimer's disease (AD) [21], epilepsy [22], dementia [23] and PD [24]. Researchers had proved that certain non-nutritive chemicals in plants viz triterpenoids and flavanoids possess antioxidant properties. The lack of effective and widely applicable pharmacological treatments in the modern therapy for neurodegenerative disorder may explain the growing interest in the traditional medicines [25]. Protective and/or rescuing treatments have also been proposed trying to suppress the possible causes of dopaminergic neurons apoptosis such as: oxidative stress, age dependent mitochondrial dysfunction, neurotoxins, decrease of neurotrophic factors, excitotoxicity, disturbances of calcium homeostasis, immunologic and infectious mechanisms [26]. Among these, oxidative stress has been suggested as playing a major role. Various factors have been recognized to increase oxidative stress in nigral dopaminergic neurons such as dopamine oxidation generating reactive oxygen species (ROS) and cytotoxic dopamine quinone; increased iron deposition; and reduced antioxidative capacity [27].

Flavonoids (Bioflavonoids)

Fig. 1.3.1Flavonoids (or bioflavonoids) (from the Latin word flavus meaning yellow) are a class of plant secondary metabolites. Over 4000 structurally unique flavonoids have been identified in plant sources (Harborne et al., 1975; Harborne, 1985a,b, 1986). Primarily recognized as the pigments responsible for the autumnal burst of hues and the many shades of yellow, orange, and red in flowers and food (Timberlake and Henry, 1986; Brouillard and Cheminant, 1988), the flavonoids are found in fruits, vegetables, nuts, seeds, herbs, spices, stems, flowers, as well as tea and red wine. They are usually subdivided according to their substituents into flavanols (a), anthocyanidins (b), and flavones, flavanones, and chalcones (c) This basic structure is comprised of two benzene rings (A and B) linked through a heterocyclic pyran or pyrone (with a double bond) ring (c) in the middle (Fig.1). comprise a large family of plant-derived compounds widely distributed in fruits and vegetables [28, 29]. There is growing evidence from human nutrition studies that the absorption and bioavailability of specific flavonoids is much higher than originally believed [29, 30]. Flavonoids are believed to exert protective as well as beneficial effects on multiple disease states, including cancer, cardiovascular disease, and neurodegenerative disorders [29,31, 32]. These physiologic benefits of flavonoids are generally thought to be derived from their antioxidant and free radical-scavenging properties [33]. Accordingly, flavonoids may also have therapeutic potential in ocular diseases. However, only four studies describing the potential effects of flavonoids on RGC death using RGC-5 transgenic cell lines or in vivo rodent models have been reported[34-35].

Clitoria Ternatea Linn (CT)

Clitoria ternatea Linn (Family Fabaceae) is commonly known as ''Butterfly pea(English), Buzrula (Arabic), Aparajit (Hindi).'' The plant is a twining evergreen herb, which will grow up to 3 m (9 ft) high, climbing over any available prop. The stems are pubescent and spindly. The compound leaves are made of three to nine oval or elliptical leaflets. The flowers (Fig. 1.2, 1.3) are 2-4 cm long and in various shades of blue with a yellow throat or pure white with a big standard petal. The fruits (Fig. 1.4) are pods, resembling thin peas. Which is widely used in traditional Indian system of medicine as a brain tonic and is believed to promote memory, intelligence and has shown beneficial effects on cognitive function [36, 37].

Fig. 1.4.2

Fig. 1.4.1

Fig. 1.4.3

A wide range of secondary metabolites including triterpenoids, flavonol glycosides, anthocyanins and steroids has been isolated from Clitoria ternatea Linn. Its extracts possess a wide range of pharmacological activities including antimicrobial, antipyretic, anti-inflammatory, analgesic, diuretic, local anesthetic, antidiabetic, insecticidal, blood platelet aggregation-inhibiting and for use as a vascular smooth muscle relaxing properties [38]. C. ternatea contains antifungal proteins and has been shown to be homologous to plant defensins, Roots, seeds and leaves of C. ternatea are commonly used in the Ayurvedic system of medicine, roots and seeds have powerful laxative effects whereas the roots are bitter, refrigerant, laxative, intellect promoting, diuretic, anthelmintic and tonic and are useful in dementia, memory enhancer, hemicrania, burning sensation, leprosy, inflammation, leucoderma, bronchitis, asthma, pulmonary tuberculosis, ascites and fever. The leaves are useful in otalgia and hepatopathy, and used in Madagascar to relieve joint pain whereas seeds are cathartic, the flowers are used to make collyrium [39, 40, 41]. Earlier experimental studies with oral intubation of Clitoria ternatea aqueous root extract to neonatal and young adult rats have shown that consumption of this extract significantly enhances spatial and passive avoidance learning and memory retention in both groups of rats as compared to age matched controls [41], and also significantly increases dendritic branching and intersections of CA3 pyramidal neurons of the hippocampus [43]. Also, earlier studies have also shown that acetylcholine (ACh) content is significantly increased in the hippocampi of young adult rats orally intubated with Clitoria ternatea aqueous root extract as compared to ACh levels in hippocampi of age matched controls [44]. earlier studies have also shown that oral intubation of Clitoria ternatea aqueous root extract to neonatal and young adult rats, also significantly increases growth of neurons of the amygdala [45]. People use different species of Clitoria as a medicinal agent to enhance fertility, to control menstrual discharge, to treat gonorrhea and as a sexual stimulant [46]. The preliminary phytochemical screening of the roots revealed the presence of alkaloids, glycosides, flavanoids, resins, saponins, phenols, triterpenes, proteins & carbohydrates [47, 48]. And because CT is enriched with bioflavonoids it would be interesting to explore the neuroprotective effect of this plant against Parkinson's disease (PD).


The Aim of The Research

hence the difficulty in obtaining a brain biopsy to monitor the parkinsonism status is Parkinsonism patient, until after the death . It is therefore imperative to develop suitable peripheral markers, which can help in the diagnosis of PD during life. That's why the aim of this research is to investigate and monitor the effect of C. ternatea plant extract on experimentally induced parkinsonism by studying its effect on Parkinson's biomarkers like Oxidative stress (OX), Total Antioxidant Capacity (TAC), poly(ADP-ribose) polymerase (PARP).

MPTP as Parkinsonism Inducer

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin precursor to MPP+, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain. It has been used to study disease models in various animal studies. The Parkinson-inducing effects of MPTP were first discovered following accidental ingestion as a result of contaminated MPPP. All evidence to date suggests that the compound selectively kills neurons in the zona compacta of the substantia nigra [7,8,17], MPTP appears to be the first neuro- toxin to selectively affect a subset of catecholaminergic neurons 17, Shortly after a five day course of MPTP, fluorescence techniques show an apparent swelling and distortion of the axons in the mgrostriatal pathway, with a loss of fluorescence of terminals in the striatum and cell bodies in the nigra 17. There is also an absence of tyrosme hydroxylase staining in the striatum.

Materials and methodology

Clitoria Ternatea Extract (CTE)


Total antioxidant Capacity (TAC)

Xanthine Oxidase (XO) Assay

Poly (ADP-ribose) polymerase (PARP) Assay

Results and Discussions



Summary and Conclusion