Parkinson's Disease: An Integrative Analysis of Pathophysiology, Genetic Susceptibility, Diagnosis, Therapeutic Strategies, and Emerging Researches
الملخص
Parkinson's disease is a chronic , degenerative and the second most prevalent neurodegenerative disorder, with a wide spectrum of clinical features, caused by a group of interaction factors , mainly , genetic and environmental factors. PD is marked by a progressive decline in dopaminergic neurotransmission in the human midbrain, as well as, aggregation of Lewy bodies. patients with PD can demonstrate a wide array of motor symptoms, including tremor, muscle rigidity, and slowed movements (bradykinesia). Genetic studies of familial forms of PD have revealed rare causative mutations in at least three genes responsible for autosomal recessive inheritance patterns.. The accurate diagnosis of Parkinson's disorder is a vital for prognostic and therapeutic reasons and is essential for all clinical research, moreover, the available medications mainly manage the dopaminergic features of the disease, however, the medications for the management of non-motor symptoms is inadequate. Advances in genotyping technology have paved the way of a high-throughput genome-wide screening of common variants in large populations offering a novel opportunities for the investigating the genetic basis of Parkinson's disease.
الكلمات المفتاحية:
Autosomal recessive
Bradykinesia, Dopaminergic Neurotransmission
, Lewy bodies
Parkinson's disease
كيفية الاقتباس
Ali Abdussalam Khalifa Alshibani. (2025). Parkinson’s Disease: An Integrative Analysis of Pathophysiology, Genetic Susceptibility, Diagnosis, Therapeutic Strategies, and Emerging Researches. مجلة جامعة بني وليد للعلوم الإنسانية والتطبيقية, 10(2), 520-536. https://doi.org/10.58916/jhas.v10i2.773
إصدار
القسم
Article
المراجع
1.
Bertram, L. and R.E. Tanzi, The genetic epidemiology of neurodegenerative disease. J Clin Invest, 2005. 115(6): p. 1449-57.
2.
Blackinton, J., et al., Formation of a stabilized cysteine sulfinic acid is critical for the mitochondrial function of the parkinsonism protein DJ-1. Journal of Biological Chemistry, 2009. 284(10): p. 6476.
3.
Brooks, D., et al., Imaging approaches to Parkinson’s disease. 2010.
4.
Bushati, N. and S. Cohen, microRNAs in neurodegeneration. Current opinion in neurobiology, 2008. 18(3): p. 292-296.
5.
Clarke, C., and Guttman, M. 2002. Dopamine agonist monotherapy in Parkinson's Disease. Science Direct. 360: 1767-1769.
6.
Brooks, D.J., Imaging approaches to Parkinson disease. J Nucl Med. 51(4): p. 596-609.
7.
Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. JAMA. 2014 Apr 23-30;311(16):1670-83
8.
Crossman, A. 2004. A hypothesis on the pathophysiological mechanisms that underlie levodopa- or dopamine agonist-induced dyskinesia in Parkinson's Disease: Implications for future strategies in treatment. Wiley InterScience. 5(2): 100-108.
9.
Deane KH, Ellis-Hill C, Playford ED, Ben-Shlomo Y, and Clarke CE. 2001. Occupational therapy for patients with Parkinson's Disease. Cochrane Database Syst Rev. 3: 2813.
10.
De Bie RMA, Katzenschlager R, Swinnen BEKS, Peball M, Lim SY, Mestre TA, Perez Lloret S, Coelho M, Aquino C, Tan AH, Bruno V, Dijk JM, Heim B, Lin CH, Kauppila LA, Litvan I, Spijker R, Seppi K, Costa J, Sampaio C, Fox SH, Silverdale MA. Update on Treatments for Parkinson's Disease Motor Fluctuations - An International Parkinson and Movement Disorder Society Evidence-Based Medicine Review. Mov Disord. 2025 May;40(5):776-794. doi: 10.1002/mds.30162. Epub 2025 Mar 8..
11.
Deng, J., et al., Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase. Proceedings of the National Academy of Sciences, 2008. 105(5): p. 1499.
12.
Foltynie T, Bruno V, Fox S, Kühn AA, Lindop F, Lees AJ. Medical, surgical, and physical treatments for Parkinson's disease. Lancet. 2024 Jan 20;403(10423):305-324.
13.
Fox SH, Katzenschlager R, Lim SY, Barton B, de Bie RMA, Seppi K, Coelho M, Sampaio C; Movement Disorder Society Evidence-Based Medicine Committee. International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson's disease. Mov Disord. 2018 Aug;33(8):1248-1266. Epub 2018 Mar 23. Erratum in: Mov Disord. 2018 Dec;33(12):1992.
14.
Goede, C., Keus, P., Kwakkel, P., and W., agenaar, R. 2OO5. The effects of physical therapy in parkinson's disease: A research synthesis. Science Direct. 82: 509-515.
15.
Goetz, C., et al., Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Movement disorders, 2008. 23(15): p. 2129-2170.
16.
Ilic, T.V., Transcranial direct current stimulation. Clinical Neurophysiology, 2008. 119(3): p. e68-e68.
17.
Hardy, J., M. Cookson, and A. Singleton, Genes and parkinsonism. The Lancet Neurology, 2003. 2(4): p. 221-228.
18.
Heron, N., et al., SAR and inhibitor complex structure determination of a novel class of potent and specific Aurora kinase inhibitors. Bioorganic & medicinal chemistry letters, 2006. 16(5): p. 1320-1323.
19.
Höglinger G; German Parkinson’s Guidelines Committee; Trenkwalder C. Diagnosis and treatment of Parkinson´s disease (guideline of the German Society for Neurology). Neurol Res Pract. 2024 Jun 6;6(1):30.
20.
Huang, Y., et al., Genetic contributions to Parkinson's disease. Brain Research Reviews, 2004. 46(1): p. 44-70.
21.
Jankovic, J. 2008. Parkinson's Disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 79:368-376.
22.
Keus SH, Munneke M, Nijkrake MJ, Kwakkel G, Bloem BR. 2009. Physical therapy in Parkinson's Disease: evolution and future challenges. Movement Disorder Society. 24(1): 1-14.
23.
Kim, S.W., et al., Recent advances in our understanding of Parkinson's disease. Drug Discovery Today: Disease Mechanisms, 2005. 2(4): p. 427-433.
24.
Larsen, J., Dupont, E., and Tandberg, E. 2009. Clinical diagnosis of Parkinson's Disease. Proposal of diagnostic subgroups classified at different levels of confidence. Wiley InterScience. 89: 242 – 251.
25.
LeWitt, P. 2008. Levodopa for the Treatment of Parkinson's Disease. The New England Journal of Medicine. 359: 2468-2476.
26.
Li, Y., et al., Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's Disease. Nat Neurosci, 2009. 12(7): p. 826-8.
27.
Mehnert, S., Reuter,I., Schepp, K., Maaser, P., Stolz, E., and Kaps, M. 2010. Transcranial sonography for diagnosis of Parkinson's Disease. BMC Neurology.10:1-7.
28.
Nijkrake MJ, Keus SH, Kalf JG, Sturkenboom IH, Munneke M, Kappelle AC, and Bloem BR. 2007. Allied health care interventions and complementary therapies in Parkinson's Disease. Parkinsonism Related Disord.13: 488-494.
29.
Peng, B. and M. Kimmel, Simulations provide support for the common disease-common variant hypothesis. Genetics, 2007. 175(2): p. 763.
30.
Poewe, W., Non-motor symptoms in Parkinson's disease. Eur J Neurol, 2008. 15 Suppl 1: p. 14-20.
31.
Pringsheim T, Day GS, Smith DB, et al. Dopaminergic Therapy for Motor Symptoms in Early Parkinson Disease Practice Guideline Summary: A Report of the AAN Guideline Subcommittee. Neurology. 2021;97(20):942-957.
32.
Ramjit, A.L., et al., The Relationship Between Anosmia, Constipation, and Orthostasis and Parkinson's Disease Duration: Results of a Pilot Study. International Journal of Neuroscience, 2010. 120(1): p. 67-70.
33.
Ramsey, C.P. and B.I. Giasson, Role of mitochondrial dysfunction in Parkinson's Disease: Implications for treatment. Drugs Aging, 2007. 24(2): p. 95-105.
34.
Saint-Cyr, J., and Trépanier, L. 2001. Neuropsychologic assessment of patients for movement disorder surgery. Wiley InterScience. 15(5): 771 – 783.
35.
Savitt, J., Dawson, V., and Dawson, T. 2006. Diagnosis and treatment of Parkinson disease: molecules to medicine. J. Clin. Invest. 116(7): 1744-1754.
36.
Schapira, A. 2005. Present and future drug treatment for Parkinson's Disease. J Neurol Neurosurg Psychiatry. 76: 1472-1478.
37.
Schwarzschild, M.A., et al., Serum urate as a predictor of clinical and radiographic progression in Parkinson disease. Arch Neurol, 2008. 65(6): p. 716-23.
38.
Seong Who Kim, Han Seok Ko1, Valina L. Dawson Ted M. Dawson. Recent advances in our understanding of Parkinson’s disease. Vol. 2, No. 4 2005.USA
39.
Sidransky, E., et al., Multicenter analysis of glucocerebrosidase mutations in Parkinson's Disease. N Engl J Med, 2009. 361(17): p. 1651-61. Starkstein, S. 2009. Anticholinergic activity and cognitive decline in Parkinson's Disease. J Neurol Neurosurg Psychiatry. 81: 160-165.
40.
Simon-Sanchez, J., et al., Genome-wide association study reveals genetic risk underlying Parkinson's Disease. Nat Genet, 2009. 41(12): p. 1308-1312.
41.
Stocchi1, F., Vacca, L., Grassini., P., Battaglia, G.,Onofrj, M., Valente., M., and Ruggieri, S. 2004. Optimizing levodopa pharmacokinetics in Parkinson's Disease: the role of COMT inhibitor. Neurological Sciences. 24(3): 217-218.
42.
Tanaka, A., Parkin-mediated selective mitochondrial autophagy, mitophagy: Parkin purges damaged organelles from the vital mitochondrial network. FEBS Lett, 2010. 584(7): p. 1386-92.
43.
Tanner CM, Ostrem JL. Parkinson's Disease. N Engl J Med. 2024 Aug 1;391(5):442-452. doi: 10.1056/NEJMra2401857. PMID: 39083773.
44.
Tintner, R., and Jankovic, J. 2003. Dopamine agonists in Parkinson's Disease. Expert Of Investing Drugs. 12(11): 1803-1820.
45.
Trempe, J., et al., SH3 Domains from a Subset of BAR Proteins Define a Ubl-Binding Domain and Implicate Parkin in Synaptic Ubiquitination. Molecular cell, 2009. 36(6): p. 1034-1047.
46.
Tsuji, S., Genetics of neurodegenerative diseases: insights from high-throughput resequencing. Hum Mol Genet, 2010.
47.
Ulmer, T. and A. Bax, Comparison of structure and dynamics of micelle-bound human -synuclein and Parkinson disease variants. Journal of Biological Chemistry, 2005. 280(52): p. 43179.
48.
Venkataramana, N.K., et al., Open-labelled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson's Disease. Transl Res, 2010. 155(2): p. 62-70.
49.
Vincenzo Bonifati. Genetics of Parkinsonism. Parkinsonism and Related Disorders 13 (2007) S233–S241. Rotterdam. The Netherlands.
50.
Wilson, M. A., et al. (2021). "Structural basis of Parkinson’s disease-linked mutations in DJ-1." Nature Communications, 12(1), 64. [DOI:10.1038/s41467-020-20375-x]
51.
Wood-Kaczmar, S. Gandhi and N.W. Wood. Understanding the molecular causes of Parkinson’s disease. TRENDS in Molecular Medicine Vol.12 No.11 Department of Molecular Neuroscience, Institute of Neurology, and National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK. 2006.
