Neurons to Genes A Comprehensive Review of Parkinson’s Disease
DOI:
https://doi.org/10.64229/zg52em90Keywords:
Mitochondrial dysfunction, Neurodegeneration, Neuroinflammation, Oxidative stress, Parkinson’s diseaseAbstract
Parkinson’s disease (PD) is an insidious neurodegenerative disease that is marked by loss of dopaminergic cells of the substantia nigra (SN) and aggregation of misfolded a-synuclein proteins. It is characterized by typical motor symptoms such as tremor, rigidity, bradykinesia, and postural instability, along with a wide range of non-motor manifestations including cognitive impairment, autonomic dysfunction, sleep disturbances, and mood disorders.The pathophysiology of PD is multifactorial, as it entails protein aggregation, mitochondrial dysfunction, oxidative stress, neuroinflammation, and genetics. Although significant advancements have been made in levodopa-based therapies and surgical interventions such as deep brain stimulation, these approaches primarily provide symptomatic relief and do not prevent disease progression. Emerging therapeutic strategies, including gene therapy, RNA-based therapeutics, immunotherapy, and stem cell interventions, are currently under investigation for their potential disease-modifying effects. Furthermore, patient-centered and precision medicine approaches are becoming increasingly important in PD management. This review integrates clinical, molecular, and therapeutic perspectives, with particular emphasis on challenges associated with bench-to-bedside translation. It also highlights the urgent need for reliable biomarkers, early diagnosis, and multidisciplinary disease-modifying strategies for future therapeutic interventions.
References
[1]Church FC. Treatment options for motor and non-motor symptoms of Parkinson’s disease. Biomolecules, 2021, 11(4), 612. DOI: 10.3390/biom11040612
[2]Pourzinal D, Brooks D, Sriram D, Mccann E, King JM, Pachana NA, et al. Best practice guidelines for the diagnosis, evaluation, and management of cognitive disorders in Parkinson’s disease. Age Ageing, 2026, 55(3), afag063. DOI: 10.1093/ageing/afag063
[3]Singh J, Singh P. In silico evaluation of elaeocarpus serratus bioactive compounds for parkinson’s disease: Network analysis and quercetin docking. International Journal of Research Publication and Reviewsv, 2025, 6(11): 4968-4987. DOI: 10.55248/GENGPI.06.1125.38174
[4]Ogunjobi TT, Gbayisomore TJ, Nneji PO, Olofin OO, Olowe EN, Gigam-Ozuzu CD, et al. Environmental epigenetics and its impacts on disease susceptibility: A comprehensive review. Medinformatics, 2024. DOI: 10.47852/bonviewMEDIN42022945
[5]Su D, Cui Y, He C, Yin P, Bai R, Zhu J, et al. Projections for prevalence of Parkinson’s disease and its driving factors in 195 countries and territories to 2050: Modelling study of Global Burden of Disease Study 2021. BMJ, 2025, 388, e080952. DOI: 10.1136/bmj-2024-080952
[6]Zhang J, Fan Y, Liang H, Zhang Y. Global, regional and national temporal trends in Parkinson’s disease incidence, disability-adjusted life year rates in middle-aged and older adults: A cross-national inequality analysis and bayesian age-period-cohort analysis based on the global burden of disease 2021. Neurological Sciences, 2025, 46(4), 1647-1660. DOI: 10.1007/s10072-024-07941-7
[7]Albin RL. Parkinson disease. Oxford University Press, 2022. DOI: 10.1093/med/9780190843014.001.0001
[8]Walusinski O. Jean-Martin Charcot (1825-1893). In Oxford Research Encyclopedia of Neuroscience. DOI: 10.1093/acrefore/9780190264086.013.546
[9]Gouda NA, Elkamhawy A, Cho J. Emerging therapeutic strategies for Parkinson’s disease and future prospects: A 2021 update. Biomedicines, 2022, 10(2), 371. DOI: 10.3390/biomedicines10020371
[10]Picca A, Guerra F, Calvani R, Romano R, Coelho-Júnior HJ, Bucci C, et al. Mitochondrial dysfunction, protein misfolding and neuroinflammation in Parkinson’s disease: Roads to biomarker discovery. Biomolecules, 2021, 11(10), 1508. DOI: 10.3390/biom11101508
[11]Meganck RM, Baric RS. Developing therapeutic approaches for twenty-first-century emerging infectious viral diseases. Nature Medicine, 2021, 27(3), 401-410. DOI: 10.1038/s41591-021-01282-0
[12]Pandey SK, Singh RK. Recent developments in nucleic acid-based therapies for Parkinson’s disease: Current status, clinical potential, and future strategies. Frontiers in Pharmacology, 2022, 13, 986668. DOI: 10.3389/fphar.2022.986668
[13]Muleiro Alvarez M, Cano-Herrera G, Osorio Martínez MF, Vega Gonzales-Portillo J, Monroy GR, Murguiondo Pérez R, et al. A comprehensive approach to parkinson’s disease: Addressing its molecular, clinical, and therapeutic aspects. International Journal of Molecular Sciences, 2024, 25(13), 7183. DOI: 10.3390/ijms25137183
[14]Dong-Chen X, Yong C, Yang X, Chen-Yu S, Li-Hua P. Signaling pathways in Parkinson’s disease: Molecular mechanisms and therapeutic interventions. Signal Transduction and Targeted Therapy, 2023, 8(1), 73. DOI: 10.1038/s41392-023-01353-3
[15]Clarkin CM, Smith DG, McGough EL, Mahler LA. Centering the person in development of a model of care for people with Parkinson’s disease: A qualitative study. Disability and Rehabilitation, 2025, 47(8), 1976-1987. DOI: 10.1080/09638288.2024.2387689
[16]Jankovic J, Lang AE. Diagnosis and assessment of Parkinson disease and other movement disorders. Bradley’s Neurology in Clinical Practice E-Book, 2021, 24, 310-333.
[17]Bologna M, Espay AJ, Fasano A, Paparella G, Hallett M, Berardelli A. Redefining bradykinesia. Movement disorders: Official Journal of the Movement Disorder Society, 2023, 38(4), 551. DOI: 10.1002/mds.29362
[18]Ganguly J, Kulshreshtha D, Almotiri M, Jog M. Muscle tone physiology and abnormalities. Toxins, 2021, 13(4), 282. DOI: 10.3390/toxins13040282
[19]Blesa J, Foffani G, Dehay B, Bezard E, Obeso JA. Motor and non-motor circuit disturbances in early Parkinson disease: Which happens first? Nature Reviews Neuroscience, 2022, 23(2), 115-128. DOI: 10.1038/s41583-021-00542-9
[20]Jankovic J, Hallett M, Okun MS, Comella CL, Fahn S. Principles and practice of movement disorders E-book. Elsevier Health Sciences, 2021.
[21]Rinaldi D. Motor and non-motor symptoms in advanced Parkinson’s disease: current insights and future directions. 2025.
[22]Lubomski M, Davis RL, Sue CM. Cognitive influences in Parkinson’s disease patients and their caregivers: Perspectives from an australian cohort. Frontiers in Neurology, 2021, 12, 673816. DOI: 10.3389/fneur.2021.673816
[23]Antelmi E, Lippolis M, Biscarini F, Tinazzi M, Plazzi G. REM sleep behavior disorder: Mimics and variants. Sleep Medicine Reviews, 2021, 60, 101515. DOI: 10.1016/j.smrv.2021.101515
[24]Mather M. Autonomic dysfunction in neurodegenerative disease. Nature Reviews Neuroscience, 2025, 26(5), 276-292. DOI: 10.1038/s41583-025-00911-8
[25]Harsh S, Rather HJ, Dwivedi A, Bala S, Velladurai P, Anantharaman S. The neuropsychology of chronic neurological disorders: A review of cognitive and emotional impairments. Cureus, 2025, 17(10), e93642. DOI: 10.7759/cureus.93642
[26]Singh J. Parkinson’s disease: Pathophysiology, current treatments, and future therapeutic approaches. RMC Global Journal, 2026, 2, 1-7. DOI: 10.25259/RMCGJ_9_2025
[27]Chahine LM, Merchant K, Siderowf A, Sherer T, Tanner C, Marek K, et al. Proposal for a biologic staging system of Parkinson’s disease. Journal of Parkinson’s Disease, 2023, 13(3), 297-309. DOI: 10.3233/JPD-225111
[28]Bouça-Machado R. Functional mobility in Parkinson’s disease. Universidade de Lisboa (Portugal), 2021.
[29]Tofaris GK. Initiation and progression of α-synuclein pathology in Parkinson’s disease. Cellular and Molecular Life Sciences, 2022, 79(4), 210. DOI: 10.1007/s00018-022-04240-2
[30]Kumar S, Rani S, Sharma S, Min H. Multimodality fusion aspects of medical diagnosis: A comprehensive review. Bioengineering, 2024, 11(12), 1233. DOI: 10.3390/bioengineering11121233
[31]Coughlin DG, Dickson DW, Josephs KA, Litvan I. Progressive supranuclear palsy and corticobasal degeneration. In Frontotemporal Dementias: Emerging Milestones of the 21st Century. Cham: Springer International Publishing, 2021, 151-176.
[32]Pitton Rissardo J, Caprara ALF. Neuroimaging techniques in differentiating parkinson’s disease from drug-induced parkinsonism: A comprehensive review. Clinics and Practice, 2023, 13(6), 1427-1448. DOI: 10.3390/clinpract13060128
[33]Guatteo E, Berretta N, Monda V, Ledonne A, Mercuri NB. Pathophysiological features of nigral dopaminergic neurons in animal models of Parkinson’s disease. International Journal of Molecular Sciences, 2022, 23(9), 4508. DOI: 10.3390/ijms23094508
[34]Jiang Y, Qi Z, Zhu H, Shen K, Liu R, Fang C, et al. Role of the globus pallidus in motor and non-motor symptoms of Parkinson’s disease. Neural Regeneration Research, 2025, 20(6), 1628-1643. DOI: 10.4103/NRR.NRR-D-23-01660
[35]Gonzalez-Robles C, Bandmann O, Schapira AHV. Neuroprotection in Parkinson disease. Neurology and Therapy, 2025, 14(5), 1747-1767. DOI: 10.1007/s40120-025-00793-z
[36]Ghiglieri V, Calabrese V, Calabresi P. Alpha-synuclein: From early synaptic dysfunction to neurodegeneration. Frontiers in Neurology, 2018, 9, 295. DOI: 10.3389/fneur.2018.00295
[37]Borghammer P. The α-synuclein origin and connectome model (SOC model) of Parkinson’s disease: Explaining motor asymmetry, non-motor phenotypes, and cognitive decline. Journal of Parkinson’s Disease, 2021, 11(2), 455-474. DOI: 10.3233/JPD-202481
[38]Chmielarz P, Domanskyi A. Alpha-synuclein preformed fibrils: A tool to understand Parkinson’s disease and develop disease modifying therapy. Neural Regeneration Research, 2021, 16(11), 2219-2221. DOI: 10.4103/1673-5374.310686
[39]Harackiewicz O, Grembecka B. The role of microglia and astrocytes in the pathomechanism of neuroinflammation in Parkinson’s disease-focus on alpha-synuclein. Journal of Integrative Neuroscience, 2024, 23(11), 203. DOI: 10.31083/j.jin2311203
[40]Huang X, Hussain B, Chang J. Peripheral inflammation and blood-brain barrier disruption: Effects and mechanisms. CNS Neuroscience & Therapeutics, 2021, 27(1), 36-47. DOI: 10.1111/cns.13569
[41]Hanna L, Poluyi E, Ikwuegbuenyi C, Morgan E, Imaguezegie G. Peripheral inflammation and neurodegeneration; a potential for therapeutic intervention in Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Egyptian Journal of Neurosurgery, 2022, 37(1), 15. DOI: 10.1186/s41984-022-00150-4
[42]Henrich MT, Oertel WH, Surmeier DJ, Geibl FF. Mitochondrial dysfunction in Parkinson’s disease__a key disease hallmark with therapeutic potential. Molecular Neurodegeneration, 2023, 18(1), 83. DOI: 10.1186/s13024-023-00676-7
[43]Imberechts D, Kinnart I, Wauters F, Terbeek J, Manders L, Wierda K, et al. DJ-1 is an essential downstream mediator in PINK1/parkin-dependent mitophagy. Brain, 2022, 145(12), 4368-4384. DOI: 10.1093/brain/awac313
[44]Kim TY, Lee BD. Current therapeutic strategies in Parkinson’s disease: Future perspectives. Molecules and Cells, 2025, 48(11), 100274. DOI: 10.1016/j.mocell.2025.100274
[45]Chen Y, Luo X, Yin Y, Thomas ER, Liu K, Wang W, et al. The interplay of iron, oxidative stress, and α-synuclein in Parkinson’s disease progression. Molecular Medicine, 2025, 31(1), 154. DOI: 10.1186/s10020-025-01208-3
[46]Singh J, Kumar D, Kaur J, et al. The rhythm of decline: Circadian disruption in neurodegeneration. Journal of Food and Drug Analysis, 2025, 33(3), 224-240. DOI: 10.38212/2224-6614.3553
[47]Luo S, Wang D, Zhang Z. Post-translational modification and mitochondrial function in Parkinson’s disease. Frontiers in Molecular Neuroscience, 2024, 16, 1329554. DOI: 10.3389/fnmol.2023.1329554
[48]Prajjwal P, Flores Sanga HS, Acharya K, Tango T, John J, Rodriguez RSC, et al. Parkinson’s disease updates: Addressing the pathophysiology, risk factors, genetics, diagnosis, along with the medical and surgical treatment. Annals of Medicine and Surgery, 2023, 85(10), 4887-4902. DOI: 10.1097/MS9.0000000000001142
[49]Masaldan S, Callegari S, Dewson G. Therapeutic targeting of mitophagy in Parkinson’s disease. Biochemical Society Transactions, 2022, 50(2), 783-797. DOI: 10.1042/BST20211107
[50]Muse ED, Chen SF, Torkamani A. Monogenic and polygenic models of coronary artery disease. Current Cardiology Reports, 2021, 23(8), 107. DOI: 10.1007/s11886-021-01540-0
[51]Wang K, Liu H, Hu Q, Wang L, Liu J, Zheng Z, et al. Epigenetic regulation of aging: implications for interventions of aging and diseases. Signal Transduction and Targeted Therapy, 2022, 7(1), 374. DOI: 10.1038/s41392-022-01211-8
[52]Wu KM, Zhang Y, Wang TT, et al. Advancing disease-modifying therapies for Parkinson’s disease: Current strategies and future directions. The Innovation, 2025. DOI: 10.1016/j.xinn.2025.101112
[53]Khan MS, Nasiripour S, Bopassa JC. Parkinson disease signaling pathways, molecular mechanisms, and potential therapeutic strategies: A comprehensive review. International Journal of Molecular Sciences, 2025, 26(13), 6416. DOI: 10.3390/ijms26136416
[54]Eldeeb MA, Thomas RA, Ragheb MA, Fallahi A, Fon EA. Mitochondrial quality control in health and in Parkinson’s disease. Physiological Reviews, 2022, 102(4), 1721-1755. DOI: 10.1152/physrev.00041.2021
[55]Erskine D, Koss D, Korolchuk VI, Outeiro TF, Attems J, McKeith I. Lipids, lysosomes and mitochondria: insights into Lewy body formation from rare monogenic disorders. Acta Neuropathologica, 2021, 141(4), 511-526. DOI: 10.1007/s00401-021-02266-7
[56]Sharma M, Burré J. α-Synuclein in synaptic function and dysfunction. Trendsin Neurosciences, 2023, 46(2), 153-166. DOI: 10.1016/j.tins.2022.11.007
[57]Le Guerroué F, Youle RJ. Ubiquitin signaling in neurodegenerative diseases: An autophagy and proteasome perspective. Cell Death & Differentiation, 2021, 28(2), 439-454. DOI: 10.1038/s41418-020-00667-x
[58]Oliveira LMA, Gasser T, Edwards R, Zweckstetter M, Melki R, Stefanis L, et al. Alpha-synuclein research: defining strategic moves in the battle against Parkinson’s disease. npj Parkinson’s Disease, 2021, 7(1), 65. DOI: 10.1038/s41531-021-00203-9
[59]Ravinther AI, Dewadas HD, Tong SR, Foo CN, Lin YE, Chien CT, et al. Molecular pathways involved in lrrk2-linked parkinson’s disease: A systematic review. International Journal of Molecular Sciences, 2022, 23(19), 11744. DOI: 10.3390/ijms231911744
[60]Usmani A, Shavarebi F, Hiniker A. The cell biology of LRRK2 in Parkinson’s disease. Molecular and Cellular Biology, 2021, 41(5), e00660-20. DOI: 10.1128/MCB.00660-20
[61]Müller-Rischart AK, Pilsl A, Beaudette P, Patra M, Hadian K, Funke M, et al. The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO. Molecular Cell, 2013, 49(5), 908-921. DOI: 10.1016/j.molcel.2013.01.036
[62]Iorio R, Celenza G, Petricca S. Mitophagy: Molecular mechanisms, new concepts on parkin activation and the emerging role of AMPK/ULK1 axis. Cells, 2021, 11(1), 30. DOI: 10.3390/cells11010030
[63]Borsche M, Pereira SL, Klein C, Grünewald A. Mitochondria and Parkinson’s disease: Clinical, molecular, and translational aspects. Journal of Parkinson’s Disease, 2021, 11(1), 45-60. DOI: 10.3233/JPD-201981
[64]Olszewska DA, McCarthy A, Soto-Beasley AI, Walton RL, Ross OA, Lynch T. PARKIN, PINK1, and DJ1 analysis in early-onset Parkinson’s disease in Ireland. Irish Journal of Medical Science, 2022, 191(2), 901-907. DOI: 10.1007/s11845-021-02563-w
[65]Vizziello M, Borellini L, Franco G, Ardolino G. Disruption of mitochondrial homeostasis: The role of PINK1 in Parkinson’s disease. Cells, 2021, 10(11), 3022. DOI: 10.3390/cells10113022
[66]Xiao B, Kuruvilla J, Tan EK. Mitophagy and reactive oxygen species interplay in Parkinson’s disease. npj Parkinson’s Disease, 2022, 8(1), 135. DOI: 10.1038/s41531-022-00402-y
[67]Kumar L, Malhotra M, Singh AP, Singh AP. Comprehensive review on Parkinson’s disease: insights into prevalence, pathophysiology, diagnosis, and multifaceted treatment approaches. Journal of Drug Delivery & Therapeutics, 2024, 14(6), 200-213. DOI: 10.22270/jddt.v14i6.6637
[68]Sahoo S, Padhy AA, Kumari V, Mishra P. Role of ubiquitin-proteasome and autophagy-lysosome pathways in α-synuclein aggregate clearance. Molecular Neurobiology, 2022, 59(9), 5379-5407. DOI: 10.1007/s12035-022-02897-1
[69]Chen R, Duffy Á, Do R. Genomics of drug target prioritization for complex diseases. Nature Reviews Genetics, 2026, 27(3), 231-245. DOI: 10.1038/s41576-025-00904-4
[70]Calabresi P, Di Lazzaro G, Marino G, Campanelli F, Ghiglieri V. Advances in understanding the function of alpha-synuclein: implications for Parkinson’s disease. Brain, 2023, 146(9), 3587-3597. DOI: 10.1093/brain/awad150
[71]Singh J, Kumar D. In vivo and in vitro perspectives in Parkinson’s disease: Mechanisms and the role of phytomedicine. Journal of Food and Drug Analysis, 2025, 33(3), 193. DOI: 10.38212/2224-6614.3557
[72]Jan A, Gonçalves NP, Vaegter CB, Jensen PH, Ferreira N. The prion-like spreading of alpha-synuclein in Parkinson’s disease: Update on models and hypotheses. International Journal of Molecular Sciences, 2021, 22(15), 8338. DOI: 10.3390/ijms22158338
[73]Vidović M, Rikalovic MG. Alpha-synuclein aggregation pathway in Parkinson’s disease: Current status and novel therapeutic approaches. Cells, 2022, 11(11), 1732. DOI: 10.3390/cells11111732
[74]Dolgacheva LP, Zinchenko VP, Goncharov NV. Molecular and cellular interactions in pathogenesis of sporadic Parkinson disease. International Journal of Molecular Sciences, 2022, 23(21), 13043. DOI: 10.3390/ijms232113043
[75]Ni A, Ernst C. Evidence that substantia nigra pars compacta dopaminergic neurons are selectively vulnerable to oxidative stress because they are highly metabolically active. Frontiers in Cellular Neuroscience, 2022, 16, 826193. DOI: 10.3389/fncel.2022.826193.
[76]Malpartida AB, Williamson M, Narendra DP, Wade-Martins R, Ryan BJ. Mitochondrial dysfunction and mitophagy in Parkinson’s disease: From mechanism to therapy. Trends in Biochemical Sciences, 2021, 46(4), 329-343. DOI: 10.1016/j.tibs.2020.11.007
[77]Calabresi P, Mechelli A, Natale G, Volpicelli-Daley L, Di Lazzaro G, Ghiglieri V. Alpha-synuclein in Parkinson’s disease and other synucleinopathies: From overt neurodegeneration back to early synaptic dysfunction. Cell Death & Disease, 2023, 14(3), 176. DOI: 10.1038/s41419-023-05672-9
[78]Prasuhn J, Davis RL, Kumar KR. Targeting mitochondrial Impairment in Parkinson’s disease: challenges and opportunities. Frontiers in Cell and Developmental Biology, 2021, 8, 615461. DOI: 10.3389/fcell.2020.615461
[79]Li Y, Li S, Wu H. Ubiquitination-proteasome system (UPS) and autophagy two main protein degradation machineries in response to cell stress. Cells, 2022, 11(5), 851. DOI: 10.3390/cells11050851
[80]Smith L, Schapira AHV. GBA variants and parkinson disease: Mechanisms and treatments. Cells, 2022, 11(8), 1261. DOI: 10.3390/cells11081261
[81]Bi M, Du X, Jiao Q, Chen X, Jiang H. Expanding the role of proteasome homeostasis in Parkinson’s disease: Beyond protein breakdown. Cell Death & Disease, 2021, 12(2), 154. DOI: 10.1038/s41419-021-03441-0
[82]Harms AS, Ferreira SA, Romero-Ramos M. Periphery and brain, innate and adaptive immunity in Parkinson’s disease. Acta Neuropathologica, 2021, 141(4), 527-545. DOI: 10.1007/s00401-021-02268-5
[83]Passaro AP, Lebos AL, Yao Y, Stice SL. Immune response in neurological pathology: Emerging role of central and peripheral immune crosstalk. Frontiers in Immunology, 2021, 12, 676621. DOI: 10.3389/fimmu.2021.676621
[84]Weiner HL. Immune mechanisms and shared immune targets in neurodegenerative diseases. Nature Reviews Neurology, 2025, 21(2), 67-85. DOI: 10.1038/s41582-024-01046-7.
[85]Latif S, Jahangeer M, Razia DM, Ashiq M, Ghaffar A, Akram M, et al. Dopamine in Parkinson’s disease. Clinica Chimica Acta, 2021, 522, 114-126.
[86]Srinivasan E, Chandrasekhar G, Chandrasekar P, Anbarasu K, Vickram AS. Karunakaran R, et al. Alpha-synuclein aggregation in Parkinson’s disease. Frontiers in Medicine, 2021, 8, 736978. DOI: 10.3389/fmed.2021.736978
[87]Rasool A, Manzoor R, Ullah K, Afzal R, Ul-Haq A, Imran H, Kaleem I, et al. Oxidative stress and dopaminergic metabolism: A major PD pathogenic mechanism and basis of potential antioxidant therapies. CNS & Neurological Disorders-Drug Targets, 2024, 23(7), 852-864. DOI: 10.2174/1871527322666230609141519
[88]Rahman A. Positron-emission tomography (PET) and single-photon-emission computed tomography (SPECT) diagnosis of neurological disorders. Bangladesh Journal of Medicine, 2024, 36(1), 3-14. DOI: 10.3329/bjm.v36i1.78589
[89]Vijiaratnam N, Simuni T, Bandmann O, Morris HR, Foltynie T. Progress towards therapies for disease modification in Parkinson’s disease. The Lancet Neurology, 2021, 20(7), 559-572. DOI: 10.1016/S1474-4422(21)00061-2
[90]Ma J, Tang Z, Wu Y, Zhang J, Wu Z, Huang L, et al. Differences in blood and cerebrospinal fluid between parkinson’s disease and related diseases. Cellular and Molecular Neurobiology, 2024, 45(1), 9. DOI: 10.1007/s10571-024-01523-z
[91]Jia F, Fellner A, Kumar KR. Monogenic Parkinson’s disease: Genotype, phenotype, pathophysiology, and genetic testing. Genes, 2022, 13(3), 471. DOI: 10.3390/genes13030471
[92]Dratch L, Azage M, Baldwin A, Johnson K, Paul RA, Bardakjian TM, et al. Genetic testing in adults with neurologic disorders: Indications, approach, and clinical impacts. Journal of Neurology, 2024, 271(2), 733-747. DOI: 10.1007/s00415-023-12058-6
[93]Cook L, Schulze J, Kopil C, Hastings T, Naito A, Wojcieszek J, et al. Genetic testing for Parkinson disease: Are we ready? Neurology: Clinical Practice, 2021, 11(1), 69-77. DOI: 10.1212/CPJ.0000000000000831
[94]Mitchell T, Lehéricy S, Chiu SY, Strafella AP, Stoessl AJ, Vaillancourt DE. Emerging neuroimaging biomarkers across disease stage in Parkinson disease: A review. JAMA Neurology, 2021, 78(10), 1262-1272. DOI: 10.1001/jamaneurol.2021.1312
[95]Hampel H, Shaw LM, Aisen P, Chen C, Lleó A, Iwatsubo T, et al. State-of-the-art of lumbar puncture and its place in the journey of patients with Alzheimer’s disease. Alzheimer’s & Dementia, 2022, 18(1), 159-177. DOI: 10.1002/alz.12372
[96]Berg D, Borghammer P, Fereshtehnejad SM, Heinzel S, Horsager J, Schaeffer E, et al. Prodromal Parkinson disease subtypes-key to understanding heterogeneity. Nature Reviews Neurology, 2021, 17(6), 349-361. DOI: 10.1038/s41582-021-00486-9
[97]Martinez TN, Greenamyre JT. Toxin models of mitochondrial dysfunction in Parkinson’s disease. Antioxidants & Redox Signaling, 2012, 16(9), 920-934. DOI: 10.1089/ars.2011.4033
[98]Mustapha M, Mat Taib CN. MPTP-induced mouse model of Parkinson’s disease: A promising direction of therapeutic strategies. Bosnian Journal of Basic Medical Sciences, 2021, 21(4), 422-433. DOI: 10.17305/bjbms.2020.5181
[99]Wang XL, Feng ST, Wang ZZ, Yuan YH, Chen NH, Zhang Y. Parkin, an E3 ubiquitin ligase, plays an essential role in mitochondrial quality control in Parkinson’s disease. Cellular and Molecular Neurobiology, 2021, 41(7), 1395-1411. DOI: 10.1007/s10571-020-00914-2
[100]Dawson TM, Ko HS, Dawson VL. Genetic animal models of Parkinson’s disease. Neuron, 2010, 66(5), 646-661. DOI: 10.1016/j.neuron.2010.04.034
[101]Coccia E, Ahfeldt T. Towards physiologically relevant human pluripotent stem cell (hPSC) models of Parkinson’s disease. Stem Cell Research & Therapy, 2021, 12(1), 253. DOI: 10.1186/s13287-021-02326-5
[102]Spathopoulou A, Edenhofer F, Fellner L. Targeting α-synuclein in Parkinson’s disease by induced pluripotent stem cell models. Frontiers in Neurology, 2022, 12, 786835. DOI: 10.3389/fneur.2021.786835
[103]Hager C, Jehanno C, Bentires-Alj M. Reactivation of multipotency in the mammary gland-a ripple in the pond and a turn of the tide. Journal of Mammary Gland Biology and Neoplasia, 2025, 30(1), 11. DOI: 10.1007/s10911-025-09586-4.
[104]Hermann DM, Bacigaluppi M, Bassetti CL, Bassotti G, Boltze J, Chan A, et al. Most prominent challenges in translational neuroscience and strategic solutions to bridge the gaps: Perspectives from an editorial board interrogation. Exploration of Neuroscience, 2025, 4, 1006106. DOI: 10.37349/en.2025.1006106
[105]Ke M, Chong CM, Zhu Q, Zhang K, Cai CZ, Lu JH, et al. Comprehensive perspectives on experimental models for Parkinson’s disease. Aging and Disease, 2021, 12(1), 223-246. DOI: 10.14336/AD.2020.0331
[106]Imani Farahani N, Lin L, Nazir S, Naderi A, Rokos L, McIntosh AR, et al. Advances in physiological and clinical relevance of hiPSC-derived brain models for precision medicine pipelines. Frontiers in Cellular Neuroscience, 2025, 18, 1478572. DOI: 10.3389/fncel.2024.1478572
[107]McComish SF, MacMahon Copas AN, Caldwell MA. Human brain-based models provide a powerful tool for the advancement of Parkinson’s disease research and therapeutic development. Frontiers in Neuroscience, 2022, 16, 851058. DOI: 10.3389/fnins.2022.851058
[108]di Biase L, Pecoraro PM, Carbone SP, Caminiti ML, Di Lazzaro V. Levodopa-induced dyskinesias in Parkinson’s disease: An overview on pathophysiology, clinical manifestations, therapy management strategies and future directions. Journal of Clinical Medicine, 2023, 12(13), 4427. DOI: 10.3390/jcm12134427
[109]Lees A, Tolosa E, Stocchi F, Ferreira JJ, Rascol O, Antonini A, et al. Optimizing levodopa therapy, when and how? Perspectives on the importance of delivery and the potential for an early combination approach. Expert Review of Neurotherapeutics, 2023, 23(1), 15-24. DOI: 10.1080/14737175.2023.2176220
[110]Stocchi F, Bravi D, Emmi A, Antonini A. Parkinson disease therapy: Current strategies and future research priorities. Nature Reviews Neurology, 2024, 20(12), 695-707. DOI: 10.1038/s41582-024-01034-x
[111]Gray R, Patel S, Ives N, Rick C, Woolley R, Muzerengi S, et al. Long-term effectiveness of adjuvant treatment with catechol-o-methyltransferase or monoamine oxidase b inhibitors compared with dopamine agonists among patients with Parkinson disease uncontrolled by levodopa therapy: The PD MED randomized clinical trial. JAMA Neurology, 2022, 79(2), 131-140. DOI: 10.1001/jamaneurol.2021.4736
[112]Jenner P, Rocha JF, Ferreira JJ, Rascol O, Soares-da-Silva P. Redefining the strategy for the use of COMT inhibitors in Parkinson’s disease: The role of opicapone. Expert Review of Neurotherapeutics, 2021, 21(9), 1019-1033. DOI: 10.1080/14737175.2021.1968298
[113]Rascol O, Fabbri M, Poewe W. Amantadine in the treatment of Parkinson’s disease and other movement disorders. The Lancet Neurology, 2021, 20(12), 1048-1056. DOI: 10.1016/S1474-4422(21)00249-0
[114]Bandopadhyay R, Mishra N, Rana R, Kaur G, Ghoneim MM, Alshehri S, et al. Molecular mechanisms and therapeutic strategies for levodopa-induced dyskinesia in parkinson’s disease: A perspective through preclinical and clinical evidence. Frontiers in Pharmacology, 2022, 13, 805388. DOI: 10.3389/fphar.2022.805388
[115]Carreño M, Gil-Nagel A, Serratosa JM, Toledo M, Rodriguez-Uranga JJ, Villanueva V. Spanish consensus on the management of concomitant antiseizure medications when using cenobamate in adults with drug-resistant focal seizures. Epilepsia Open, 2024, 9(3), 1051-1058. DOI: 10.1002/epi4.12936
[116]Starr PA. Placement of deep brain stimulators into the subthalamic nucleus or Globus pallidus internus: technical approach. Stereotactic and Functional Neurosurgery, 2002, 79(3-4), 118-145. DOI: 10.1159/000070828
[117]Patel DM, Walker HC, Brooks R, Omar N, Ditty B, Guthrie BL. Adverse events associated with deep brain stimulation for movement disorders: Analysis of 510 consecutive cases. Operative Neurosurgery, 2015, 11 (1), 190-199. DOI: 10.1227/NEU.0000000000000659
[118]Limousin P, Foltynie T. Long-term outcomes of deep brain stimulation in Parkinson disease. Nature Reviews Neurology, 2019, 15(4), 234-242. DOI: 10.1038/s41582-019-0145-9
[119]Starr PA, Vitek JL, Bakay RA. Ablative surgery and deep brain stimulation for Parkinson’s disease. Neurosurgery, 1998, 43(5), 989-1013; discussion 1013-1015. DOI: 10.1097/00006123-199811000-00001
[120]Podder S, Gupta VR, Khator S, Koley R, Goswami SR. Fusion of blockchain and artificial intelligence of things in E-healthcare. In AIoT. Auerbach Publications. 2025, 57-98.
[121]Hooper AK, Okun MS, Foote KD, Fernandez HH, Jacobson C, Zeilman P, et al. Clinical cases where lesion therapy was chosen over deep brain stimulation. Stereotactic and Functional Neurosurgery, 2008, 86(3), 147-152. DOI: 10.1159/000120426
[122]Bett S, Igiraneza D. The role of rehabilitation in improving quality of life of patient with Parkinson’s disease: A literature review. 2021.
[123]Weise D, Claus I, Dresel C, Kalbe E, Liepelt-Scarfone I, Lorenzl S, et al. Multidisciplinary care in Parkinson’s diseas. Journal of Neural Transmission, 2024, 131(10), 1217-1227. DOI: 10.1007/s00702-024-02807-w
[124]Atalar MS, Oguz O, Genc G. Hypokinetic dysarthria in Parkinson’s disease: A narrative review. The Medical Bulletin of Sisli Etfal Hospital, 2023, 57(2), 163-170. DOI: 10.14744/SEMB.2023.29560
[125]Baldanzi C, Crispiatico V, Foresti S, Groppo E, Rovaris M, Cattaneo D, et al. Effects of intensive voice treatment (The Lee Silverman Voice Treatment [LSVT LOUD]) in subjects with multiple sclerosis: A pilot study. Journal of Voice, 2022, 36(4), 585. e1-585. e13. DOI: 10.1016/j.jvoice.2020.07.025
[126]Subramanian I, Ricciardi L, Schrag A, Appel-Cresswell S, Kola S, Domingos JM, et al. A holistic wellness prescription for Parkinson’s disease: Evidence-based perspectives and unmet needs. Movement Disorders Clinical Practice, 2026, 13(3), 631-646. DOI: 10.1002/mdc3.70381
[127]Iłowiecka K, Glibowski P, Skrzypek M, Styk W. The long-term dietitian and psychological support of obese patients who have reduced their weight allows them to maintain the effects. Nutrients, 2021, 13(6), 2020. DOI: 10.3390/nu13062020
[128]Iqubal A, Iqubal MK, Khan A, Ali J, Baboota S, Haque SE. Gene therapy, a novel therapeutic tool for neurological disorders: current progress, challenges and future prospective. Current Gene Therapy, 2020, 20(3), 184-194. DOI: 10.2174/1566523220999200716111502
[129]Pattali R, Mou Y, Li XJ. AAV9 vector: A Novel modality in gene therapy for spinal muscular atrophy. Gene Therapy, 2019, 26(7-8), 287-295. DOI: 10.1038/s41434-019-0085-4
[130]Khan MS. Gene therapy: Current trends and future prospects in treating genetic disorders. Multidisciplinary Journal of Biochemistry, 2024, 1(1), 72-81.
[131]Velikic G, Maric DM, Maric DL, Supic G, Puletic M, Dulic O, et al. Harnessing the stem cell niche in regenerative medicine: innovative avenue to combat neurodegenerative diseases. International Journal of Molecular Sciences, 2024, 25(2), 993. DOI: 10.3390/ijms25020993
[132]Hussen BM, Taheri M, Yashooa RK, Abdullah GH, Abdullah SR, Kheder RK, et al. Revolutionizing medicine: recent developments and future prospects in stem-cell therapy. International Journal of Surgery, 2024, 110(12), 8002-8024. DOI: 10.1097/JS9.0000000000002109
[133]Rani S, Tuteja M. Chaperones as potential pharmacological targets for treating protein aggregation illness. Current Protein & Peptide Science, 2025, 26(6), 451-466. DOI: 10.2174/0113892037338028241230092414
[134]Dhariwal R, Jain M, Mir YR, Singh A, Jain B, Kumar P, et al. Targeted drug delivery in neurodegenerative diseases: the role of nanotechnology. Frontiers in Medicine, 2025, 12, 1522223. DOI: 10.3389/fmed.2025.1522223
[135]Bajan S, Hutvagner G. RNA-based therapeutics: from antisense oligonucleotides to miRNAs. Cells, 2020, 9(1), 137. DOI: 10.3390/cells9010137
[136]Choonara YE, Pillay V, Du Toit LC, Modi G, Naidoo D, Ndesendo VMK, et al. Trends in the molecular pathogenesis and clinical therapeutics of common neurodegenerative disorders. International Journal of Molecular Sciences, 2009, 10(6), 2510-2557. DOI: 10.3390/ijms10062510
[137]Gadhave DG, Sugandhi VV, Jha SK, Nangare SN, Gupta G, Singh SK, et al. Neurodegenerative disorders: Mechanisms of degeneration and therapeutic approaches with their clinical relevance. Ageing Research Reviews, 2024, 99, 102357. DOI: 10.1016/j.arr.2024.102357
[138]Zündorf G, Reiser G. Calcium dysregulation and homeostasis of neural calcium in the molecular mechanisms of neurodegenerative diseases provide multiple targets for neuroprotection. Antioxidants & Redox Signaling, 2011, 14(7), 1275-88. DOI: 10.1089/ars.2010.3359
[139]Cummings J. Disease modification and Neuroprotection in neurodegenerative disorders. Translational Neurodegeneration, 2017, 6, 25. DOI: 10.1186/s40035-017-0096-2
[140]Seyhan AA. Lost in translation: the valley of death across preclinical and clinical divide-identification of problems and overcoming obstacles. Translational Medicine Communications, 2019, 4(1), 18. DOI: 10.1186/s41231-019-0050-7
[141]Loewa A, Feng JJ, Hedtrich S. Human disease models in drug development. Nature Reviews Bioengineering, 2023, 1-15. DOI: 10.1038/s44222-023-00063-3
[142]Subramanyam M, Goyal J. Translational biomarkers: From discovery and development to clinical practice. Drug Discovery Today: Technologies, 2016, 21, 3-10. DOI: 10.1016/j.ddtec.2016.10.001
[143]Buzhor E, Leshansky L, Blumenthal J, Barash H, Warshawsky D, Mazor Y, et al. Cell-based therapy approaches: The hope for incurable diseases. Regenerative Medicine, 2014, 9(5), 649-672. DOI: 10.2217/rme.14.35
[144]Moradi S, Mahdizadeh H, Šarić T, Kim J, Harati J, Shahsavarani H, et al. Research and therapy with induced pluripotent stem cells (iPSCs): Social, legal, and ethical considerations. Stem Cell Research & Therapy, 2019, 10(1), 341. DOI: 10.1186/s13287-019-1455-y
[145]Cohen MH. Future medicine: ethical dilemmas, regulatory challenges, and therapeutic pathways to health care and healing in human transformation. University of Michigan Press, 2009.
[146]Greener M. The good, the bad and the ugly red tape of biomedical research. How could regulators lower bureaucratic hurdles in clinical research without compromising the safety of patients? EMBO Reports, 2009, 10(1), 17-20. DOI: 10.1038/embor.2008.237
[147]Kepplinger EE. FDA’s Expedited approval mechanisms for new drug products. Biotechnology Law Report, 2015, 34(1), 15-37. DOI: 10.1089/blr.2015.9999
[148]Luyckx VA. Ethical challenges of clinical innovations and medical progress. Nephrology Dialysis Transplantation, 2024, 39(9), 1375-1377. DOI: 10.1093/ndt/gfae067
[149]Waldman SA, Terzic A. Clinical and translational science: From bench-bedside to global village. Clinical and Translational Science, 2010, 3(5), 254-257. DOI: 10.1111/j.1752-8062.2010.00227.x
[150]Rivera SC, Kyte DG, Aiyegbusi OL, Slade AL, McMullan C, Calvert MJ. The impact of patient-reported outcome (PRO) data from clinical trials: A systematic review and critical analysis. Health and Quality of Life Outcomes, 2019, 17(1), 156. DOI: 10.1186/s12955-019-1220-z
[151]Hunter C, Chew-Graham C, Langer S, Stenhoff A, Drinkwater J, Guthrie E, et al. A qualitative study of patient choices in using emergency health care for long-term conditions: The importance of candidacy and recursivity. Patient Education and Counseling, 2013, 93(2), 335-341. DOI: 10.1016/j.pec.2013.06.001
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