Assignment ID-3068253.FIN

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Nov 24, 2024

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1 Parkinson’s Lab Report Student Affiliation Professor Course Date

2 Parkinson’s Lab Report Objective The goal of this study is to examine whether or not the green tea catechin epigallocatechin gallate can slow the death of neurons caused by the alpha-synuclein protein in people with Parkinson's disease. Hypothesis The alpha-synuclein proteins have a high concentration in Parkinson's disease, causing neurological damage. However, epigallocatechin gallate reduces the permeability of the protein, hence a reduction in the absorbance rate in the brain membrane resulting in Parkinson’s management. Background What are the symptoms of Parkinson’s disease? Parkinson's is a neurological disorder that causes tremors, rigidity, and poor motor coordination and balance ( Shah et al., 2020) . The initial symptoms are usually mild and gradually worsen. As their condition worsens, people may have difficulty speaking and moving. As a result of the condition, people may experience behavioral and cognitive changes, sleep problems, depressive symptoms, cognitive impairment, and fatigue. Patients with Parkinson's disease frequently exhibit a Parkinsonian gait, which includes a forward-leaning posture, shortened stride length, rapid cadence, and decreased arm swing amplitude. Individuals may struggle to initiate or maintain movement. The vast majority of manifestations are unilateral, affecting only one side or limb. As the viral infection progresses, it spreads bilaterally. The severity of symptoms may differ between the two sides. How is it currently diagnosed and treated ?

3 No blood tests or laboratory examinations are available to diagnose non-genetic Parkinson's disease at the moment (Thaler et al., 2020). Medical practitioners typically conduct a neurological examination and review the patient's medical records to establish a diagnosis for a given ailment. Levodopa is the primary pharmacological agent used to treat Parkinson's disease. Neurons facilitate levodopa conversion to dopamine as a compensatory mechanism for its neurodegenerative effects. Carbidopa is frequently used in conjunction with levodopa. Carbidopa is a valuable medication that can reduce the amount of levodopa required to alleviate symptoms. It prevents or reduces side effects such as nausea, vomiting, hypotension, and agitation. Individuals who have Parkinson's disease should not stop taking levodopa without first consulting with their doctor. If the medication is abruptly discontinued, immobilization and respiratory distress may occur. Other therapeutic drug classes include dopamine agonists, enzyme inhibitors, amantadine, and anticholinergic drugs. Write a short paragraph about alpha–Synuclein and its role in PD. Parkinson's disease (PD) and the neuronal protein synuclein are linked, according to genetic and neuropathological evidence. The general public believes that protofibrils are harmful entities that disrupt cellular homeostasis and cause neurodegeneration by modulating various intracellular targets, including synaptic function. Multiple roles for synuclein in Parkinson's disease cause have been proposed (Chen et al., 2019). Furthermore, the excreted -synuclein protein could harm neighboring cells by promoting adhesion and allowing pathological conditions to spread. Therapeutic approaches that mitigate the negative effects of protein misregulation show promise in the treatment of synucleinopathies like Parkinson's disease. The amount of -synuclein found in all Parkinson's disease cases is unknown.

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4 What is the principle of separating protein mixture using size exclusion and ion exchange chromatography? Ion-exchange chromatography is a chromatographic technique that uses molecular size differences to separate macromolecules ( Kristl et al., 2019) . The procedure employs dextran- based materials. The aforementioned technique determines a protein's molecular weight and decreases the salt concentration in protein solutions. What is EGCG? Catechin is the plant-derived compound epigallocatechin gallate (EGCG). Catechins are phytochemicals found in a wide variety of plant species ( Valencia-Hernández et al., 2023) . They are also known as polyphenols. Antioxidants with high antioxidant activity, such as EGCG and other catechins, can protect cells from free radical damage. Endogenous free radicals are reactive particles produced by the human body. Excess amounts can be harmful to your cells. Consuming antioxidant-rich foods, such as catechins, may help reduce free radical damage. Anti- inflammatory and disease-preventing effects of catechins like epigallocatechin gallate (EGCG) have been demonstrated for a variety of chronic conditions. EGCG (epigallocatechin gallate), a naturally occurring compound, can be found in various plant-based foods. However, it is available commercially as a dietary supplement, most commonly as an extract. Steps Results The absorbance of synuclein shown by the chromatograph software that had not been treated with epigallocatechin gallate was noticeably higher than that shown by the absorbance of synuclein shown by the other chromatograph software. The absorbance of the protein was measured to be approximately 650 mAU, and the elution volume was measured to be

5 approximately 740 mL as a result. The absorbance of the synuclein protein decreased to approximately 92mAU in a matching elution volume of 360mL after adding epigallocatechin gallate to the mixture. The previous value was significantly higher than this, a significant drop. Fig 1: a picture showing the absorbance of alpha-synuclein in a chromatograph elution volume without epigallocatechin gallate .

6 Fig 2: a picture showing the absorbance of alpha-synuclein in a chromatograph elution volume with epigallocatechin gallate . Discussion The presence of Lewy bodies in Parkinson's disease (PD) is distinguished by the buildup and clustering of fibrillar aggregates of alpha-synuclein (-syn) protein. Specific individuals believe that the deconstruction of -synuclein fibrils that have already formed could be a viable therapeutic approach for Parkinson's disease. According to laboratory research, epigallocatechin gallate (EGCG), a polyphenol present in green tea, has been found to degrade -syn fibrils into inert amorphous clusters. Nonetheless, the scientific community has yet to understand the fundamental molecular mechanisms behind this phenomenon comprehensively. The results indicate that epigallocatechin gallate substantially impedes the assimilation of synuclein protein. The destabilization of -syn fibrils depends on the hydrophobic and hydrogen-bonding

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7 interactions between EGCG and said fibrils. The compound known as Epigallocatechin gallate (EGCG), a highly effective antioxidant present in green tea, has demonstrated the ability to impede the attachment of membranes and the permeability of oligomers of -syn. This, in turn, reduces their cytotoxicity without any changes to their size distribution or secondary structure. The absence of a prescribed set of instructions for the required course of action could have resulted in the experiment's failure. It is possible that an error was made without detection. There is a possibility of encountering errors during the experiment because the procedure is a simulation. Conclusion In conclusion, epigallocatechin gallate has therapeutic effects on the degenerative action of synuclein protein in Parkinson's disease. Epigallocatechin gallate reduces the buildup and clustering of alpha-synuclein (-syn) fibrillar protein aggregates. Real World Application Studies have demonstrated that the antioxidants present in green tea extract, specifically EGCG, can protect neuronal cells from oxidative stress. Implementing this protective measure reduces the likelihood of developing Parkinson's disease, Alzheimer's disease, dementia, and cognitive decline. The polyphenols present in green tea have been found to inhibit the retrograde flow of dopamine and promote its widespread distribution throughout the brain. The consumption of green tea has been found to alleviate the symptoms of Parkinson's disease, specifically tremors, and rigidity. EGCG has been found to provide additional health advantages that have aided in the amelioration of various health concerns. The anti-cancer properties of EGCG are attributed to its capacity to modify various mechanisms implicated in the advancement of cancer. The

8 aforementioned factors encompass the activity of carcinogens, formation of tumors, cellular proliferation, angiogenesis, and apoptosis. The consumption of EGCG as a supplement has been shown to enhance the quality and motility of sperm in males. This intervention can improve female fertility, oocyte and embryo quality, and clinical pregnancy rates.

9 Reference Chen, B., Wen, X., Jiang, H., Wang, J., Song, N., & Xie, J. (2019). Interactions between iron and α-synuclein pathology in Parkinson's disease. Free Radical Biology and Medicine , 141 , 253-260. Kristl, A., Lokošek, P., Pompe, M., & Podgornik, A. (2019). Effect of pressure on the retention of macromolecules in ion exchange chromatography. Journal of Chromatography A , 1597 , 89-99. SHAH, A. A., KASHYAP, K., & GUPTA, A. (2020). Parkinson’s Disease: An Introduction to the Causes and Management Strategies. International Journal of Pharmaceutical Research , 12 (4). Thaler, A., Shenhar-Tsarfaty, S., Shaked, Y., Gurevich, T., Omer, N., Bar-Shira, A., ... & Mirelman, A. (2020). Metabolic syndrome does not influence the phenotype of LRRK2 and GBA related Parkinson’s disease. Scientific Reports , 10 (1), 9329. Valencia-Hernández, L. J., Ascacio-Valdés, J. A., Wong-Paz, J. E., Khan, H., & Aguilar, C. N. (2023). Immune Booster Property of Epigallocatechin-3-Gallate and Catechin. In Nutraceuticals and Functional Foods in Immunomodulators (pp. 291-312). Singapore: Springer Nature Singapore.

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Assignment ID-3068253.FIN

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