Parkinson's Disease and Gene Expression

Abstract and Acknowledgements

In this project, a literature review of studies on Parkinson's disease worldwide has been included. The aforementioned studies are about the treatment of Parkinson's disease, gene expression, and alternative methods.

Introduction

Parkinson's disease is a neurodegenerative disease that caused the loss of nerve cells responsible for the production of dopamine (C2H11NO2) in the area called substantia nigra in the brain firstly defined by James Parkinson. Dopamine chemical is a neurotransmitter responsible for signal transduction between the brain and nerve cells.

Bradykinesia, defined as the slowing of movements in dopamine deficiency or injury, leads to resting tremors, postural instability, and abnormal movements, which are defined as the absence of movement. As the loss of nerve cells is slow, it is usually seen in later ages and is more common in men It is a chronic disease. Although it is still being investigated what causes the loss of these nerve cells, it is thought to be caused by environmental factors and genetic disorders.

Types of Parkinson's Disease

There are two types of Parkinsonism as primary parkinsonism and secondary parkinsonism in Parkinson's disease. Primary parkinsonism is called as idiopathic Parkinson’s disease. That means the cause of the disease is unknown. This type of Parkinsonism is intended to use drugs that work to increase the amount of dopamine in the brain or to change the dopamine.

On the other hand, cause of the Secondary Parkinsonism is usually known and does not respond well to dopaminergic drugs. This is an important difference in helping to distinguish secondary parkinsonism from primary parkinsonism. Cause of the Secondary Parkinsonism is usually known and does not respond well to dopaminergic drugs. This is an important difference in helping to distinguish secondary parkinsonism from primary parkinsonism. Drug-induced Parkinsonism, Vascular Parkinsonism, Normal Pressure Hydrocephalus (NSA), Corticoscopic degeneration (CBD), Progressive Supranuclear (PSP), and Multiple System Atrophy (MSA) are the known causes of secondary parkinsonism. (Fénelon G)

Treatments Of Parkinson’s Disease

Although there is no clear treatment for Parkinson's disease today, the intended treatment is that the patient is able to perform his / her personal work independently. The important is that these conditions are provided and symptoms are controlled. For this, drugs are used that like contribute to dopamine deficiency, a dopamine-like effect, and prevent the breakdown of dopamine in the brain. Such these drugs include levodopa. Levodopa is converted to dopamine in the human body and brain.

In addition, physical therapy practices are important for patients' well-being and it provides eases for patients to adapt to daily life.

Adenosine A2A Antagonist

Researchers tested the A2A receptor antagonist KW-6002 for antiparkinsonian activity in primates that are given MTPT (the chemical that creates the Parkinson effect). L-Dopa is a common treatment that causes complications, including loss of drug efficacy and the onset of dyskinesia. They can increase antiparkinsonian activity when KW-600 and L-dopa are applied together. This means KW-600 can reduce L-Dopa dosage. Consequently, this study presents that the A2A receptor antagonist is an antiparkinson agent that no cause any dyskinesia or complications.

Treatment of COMT-inhibitors (Catechol-O-methyl transferase inhibitors)

COMT-inhibitor therapy aims to increase the effect of levodopa on Parkinson’s disease patients and reduce off time. In this study, the efficacy and safety of COMT inhibitors that are tolcapone, and entacapone against placebo were investigated.

The results showed that entacapone shortened the off-time compared to placebo. Tolcapone reduced more the off time and gave more meaningful results In addition to positive results, tolcapone diarrhea, entacapone increased constipation and dizziness. Both of them caused nausea, vomiting, and dyskinesia side effects. Another negative result is that the tolcapone causes three cases of fatal hepatic toxicity. The negative results have led to concerns about the reliability of tolcapone.

Kinesiotherapy

In this study, the effect of kinesiotherapy on Parkinson’s disease was investigated. Manual Muscle Test (MMT) was applied to Parkinson’s disease patients who continued to use medication. Significant results were obtained from the muscle strength of the patients who received kinesiotherapy. These results have shown that kinesiotherapy had a positive effect on Parkinson’s disease.

Gene Therapy

Pharmacological treatments be useless in long-term Parkinson’s disease and consequently, patients need deep brain stimulation (DBS). Since the underlying pathogenic process cannot be altered after DBS, the motor symptoms of patients cannot be fully treated and patients continue to be in the medical treatment process. To control symptoms or pathogenic corrections are aimed with gene therapy. Comment by [email protected]: Bu kısmın hepsi bir makaleden mi alındı? Buraya bi başka makleden de alıntı yapıp referansı zenginleştirelim.

It is necessary to know the necessary temporal and spatial properties of the gene expression and the pathogenesis of the disease. The vectors in this treatment encircle the blood-brain barrier, indicate the anatomical regions for therapy, and avoid areas where transgene expression is not required.

This study focused on the application of gene therapy to the relevant brain region for Parkinson's disease patients. As a result, infiltration to border areas and perivascular spaces have prevented in the continued studies. In addition, complete transduction of the targeted structure has been achieved. Finally, it is thought that developing technology will make a great contribution to this field.

Vitamin C, Vitamin E and Karoten

In a study the effects of Vitamin C, Vitamin E and Karoten intake on Parkinson’s disease showed Vitamin E protects against Parkinson’s disease but Vitamin C and karoten have no an effect like Vitamin E. Comment by [email protected]: Bu kısım için referans koymamışsın.birden fazla referans olursa iyi olur.

In this study, it has been shown that the intake of foods rich in antioxidant vitamin E may have a neuroprotective effect, also known as neuron protection, and hence prevent the development of Parkinson’s disease. However, taking high doses of vitamin E does not have any meaningful results. In addition, it has been shown that synthetic E vitamins have more bioactivity than natural vitamin E vitamins. In another study, it was shown that vitamin E intake did not delay the need for levodopa. After these contradictory results, a larger study was needed.

No significant results were obtained for vitamin C and carotene intake. In other words, vitamin C and carotene have no significant effect on Parkinson’s disease. It is considered that vitamin C cannot have a neuroprotective effect because of its dissolution in water.

Conclusion

Although many studies have been conducted on Parkinson's disease, the results are generally left unfinished. For this reason, although the second most common neurodegenerative disease in the world, there is still no clear treatment for Parkinson's disease. Many active substances which are thought to have an effect on Parkinson's disease have been subjected to experimental studies. Unfortunately, very significant results could not be obtained.

The aim of today's treatment of Parkinson's disease patients is to keep the patient's living conditions at the optimum level. Pharmacological and physiotherapeutic treatments are applied for that the patient can meet their own needs.

In pharmacological studies, it is aimed to minimize the off time of the patients and to improve motor disorders. However, the difficulties encountered in the studies are that cause of the disease is not known. Because of that reason, many gene expression analyses were also performed to search for answers to the question that 'Parkinson's disease is genetic?” The studies about this topic have increased in recent years with increasing technology.

References

1. Alastair J.J. Wood, M. (1993, Sep). Treatment of Parkinson's Disease. Retrieved from The New England Journal Of Medicine: https://www.nejm.org/doi/full/10.1056/NEJM199309303291408
2. Amar D, S. R. (2017, May). Series GSE99039. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE99039
3. Beaulieu JM, G. R. (2011, Feb 08). The physiology, signaling, and pharmacology of dopamine receptors. Retrieved from NCBI: https://www.ncbi.nlm.nih.gov/pubmed/21303898/
4. Bogetofte H, R. B.-L.-M. (2017, Jun). Series GSE99142. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE99142
5. Bogetofte H, R. B.-L.-M. (2017, Jun). Series GSE99471. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE99471
6. Cowley, S. A. (2017, Jun). Series GSE99473. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE99473
7. Deane K.H., S. S. (2004, Oct 18). Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson's disease. Retrieved from NCBI: https://www.ncbi.nlm.nih.gov/pubmed/15495119
8. Emborgt M.E., C. M. (2007, March). Subthalamic Glutamic Acid Decarboxylase Gene Therapy: Changes in Motor Function and Cortical Metabolism. Retrieved from Sage Journals: https://journals.sagepub.com/doi/full/10.1038/sj.jcbfm.9600364
9. Ertan S. (2005, Jan). Parkinson Hastalığının Klinik Özellikleri. Retrieved from CTF: http://www.ctf.edu.tr/stek/pdfs/42/4221.pdf
10. Etminan M., G. S. (2005, Jun). Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson's disease: a meta-analysis. Retrieved from Science Direct: https://www.sciencedirect.com/science/article/pii/S1474442205700971
11. Fénelon G, M. H. (2003, May). Secondary parkinsonian syndromes. Retrieved from NCBI: https://www.ncbi.nlm.nih.gov/pubmed/12773887
12. Fernandes HJ, H. E.-M. (2013, Dec). Series GSE53424. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53424
13. Fernandes HJ, H. E.-M. (2013, Dec). Series GSE53425. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53425
14. Fernandes HJ, H. E.-M. (2013, Dec). Series GSE53426. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53426
15. Fox S.H., K. R. (2018, March 23). International Parkinson and movement disorder society evidence‐based medicine review: Update on treatments for the motor symptoms of Parkinson's disease. Retrieved from Wiley Online Library: https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.27372
16. Haenseler W, Z. F.-M. (2016, Nov). Series GSE89878. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89878
17. Haenseler W, Z. F.-M. (2016, Nov). Series GSE89883. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89883
18. Kanda T., J. M. (2004, Oct 08). Adenosine A2A Antagonist: A novel antiparkinsonian agent that does not provoke dyskinesia in Parkinsonian monkeys. Retrieved from Wiley Online Library: https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.410430415
19. Kouroupi G, T. E. (2017, Apr). Series GSE84684. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE84684
20. Kumaran R, v. d. (2011, Jul). Series GSE28894. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE28894
21. Magrinelli F, P. A. (2016, Jun 06). Pathophysiology of Motor Dysfunction in Parkinson's Disease as the Rationale for Drug Treatment and Rehabilitation. Retrieved from NCBI: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913065/
22. Oliveira SA, F. J. (2011, Sep). Series GSE16658. Retrieved from Gen Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16658
23. Patani R, L. P. (2014, Dec). Series GSE34865. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE34865
24. Poewe W. (2009, Feb). Treatments for Parkinson disease—past achievements and current clinical needs. Retrieved from Neurology: http://n.neurology.org/content/72/7_Supplement_2/S65.short
25. Sally A Cowley, H. W. (2016, Nov). Series GSE89886. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89886
26. Sally A Cowley, S. C. (2016, Feb). Series GSE77664. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77664
27. Sandor C, R. P.-M. (2016, Feb). Series GSE77662. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77662
28. Sandor C, R. P.-M. (2016, Feb). Series GSE77663. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77663
29. Schulze M, R. M. (2018, Oct). Series GSE110716. Retrieved from Geo Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE110716
30. Schulze M, R. M. (2018, Oct). Series GSE110717. Retrieved from Gen Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE110717
31. Schulze M, R. M. (2018, Oct). Series GSE110718. Retrieved from Gen Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE110718
32. Schulze M, S. A. (2018, Oct). Series GSE110720. Retrieved from Gen Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE110720
33. Shehadeh LA, Y. K. (2010, Feb). Series GSE18838. Retrieved from Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE18838
34. Sherer T.B. (2011, Apr 20). Biomarkers for Parkinson’s Disease. Retrieved from Science Translational Medicine: http://stm.sciencemag.org/content/3/79/79ps14
35. Soreq L, B. H. (2018, May). Series GSE38385. Retrieved from Gen Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38385
36. Stacy S. Wu, F. S. (2005, Sep). Treatment of Parkinson’s Disease. Retrieved from Springer Link: https://link.springer.com/article/10.2165/00023210-200519090-00001#Sec2
37. Sudhakar V., R. R. (2018). Gene Therapy for Parkinson's Disease. Retrieved from Karger: https://www.karger.com/Article/Abstract/481109
38. Tanović E., T.-T. A.-V. (2018, Jun 08). Effects of kinesiotherapy on muscle strengthening in patients. Retrieved from ljkzedo: http://ljkzedo.ba/wordpress/wp-content/uploads/2018/11/08-Tanovic-970-A.pdf