Болезнь Паркинсона: Патогенез, биомаркеры и новые методы лечения
DOI:
https://doi.org/10.53498/pn96qn05Ключевые слова:
болезнь Паркинсона, биомаркеры, нейродегенерация, генетические факторы риска, эпидемиологияАннотация
Болезнь Паркинсона — второе по распространенности нейродегенеративное заболевание после болезни Альцгеймера. Прогнозируется, что ее заболеваемость будет резко возрастать по мере старения населения мира. Несмотря на значительные достижения в области нейронауки и иммунологии, эффективные методы лечения, изменяющие течение болезни, остаются труднодостижимыми. Однако недавние прорывы в области генетики, иммунологии, разработки биомаркеров и аналитики на основе искусственного интеллекта меняют наше понимание и подход к болезни Паркинсона. В данной статье обобщены современные знания об эпидемиологии болезни Паркинсона, патогенезе, роли генетических и средовых факторов риска, расширяющемся спектре биомаркеров и технологий ранней диагностики, а также последних достижениях в области клинической терапии с акцентом на профессиональную практику и трансляционные перспективы.
Библиографические ссылки
1. Su, D., Cui, Y., He, C., Yin, P., Bai, R., Zhu, J., Feng, T. (2025). 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, 388. https://doi.org/10.1136/bmj-2024-080952
2. Chaudhuri, K. R., Azulay, J. P., Odin, P., Lindvall, S., Domingos, J., Alobaidi, A., Kandukuri, P. L., Chaudhari, V. S., Parra, J. C., Yamazaki, T., Oddsdottir, J., Wright, J., & Martinez-Martin, P. (2024). Economic Burden of Parkinson's Disease: A Multinational, Real-World, Cost-of-Illness Study. Drugs - real world outcomes, 11(1), 1–11. https://doi.org/10.1007/s40801-023-00410-1
3. Li, X., Chen, C., Pan, T., Zhou, X., Sun, X., Zhang, Z., Chen, X. (2024). Trends and hotspots in non-motor symptoms of Parkinson’s disease: a 10-year bibliometric analysis. Frontiers in Aging Neuroscience, 16, 1335550. https://doi.org/10.3389/fnagi.2024.1335550
4. Gökçal, E., Gür, V. E., Selvitop, R., Babacan Yildiz, G., Asil, T. (2017). Motor and Non-Motor Symptoms in Parkinson's Disease: Effects on Quality of Life. Noro psikiyatri arsivi, 54(2), 143–148. https://doi.org/10.5152/npa.2016.12758
5. Huang, Y., Wei, J., Cooper, A., & Morris, M. J. (2022). Parkinson's disease: From genetics to molecular dysfunction and targeted therapeutic approaches. Genes & diseases, 10(3), 786–798. https://doi.org/10.1016/j.gendis.2021.12.015
6. Luo, Y., Xiang, Y., Liu, J., Hu, Y., Guo, J. (2025). A Multi-omics Framework Based on Machine Learning as a Predictor of Cognitive Impairment Progression in Early Parkinson's Disease. Neurology and therapy, 14(2), 643–658. https://doi.org/10.1007/s40120-025-00716-y
7. Wang, Q., Gu, X., Yang, L., Jiang, Y., Zhang, J., He, J. (2024). Emerging perspectives on precision therapy for Parkinson's disease: multidimensional evidence leading to a new breakthrough in personalized medicine. Frontiers in aging neuroscience, 16, 1417515. https://doi.org/10.3389/fnagi.2024.1417515
8. Luo, Y., Qiao, L., Li, M., Wen, X., Zhang, W., Li, X. (2025). Global, regional, national epidemiology and trends of Parkinson's disease from 1990 to 2021: findings from the Global Burden of Disease Study 2021. Frontiers in aging neuroscience, 16, 1498756. https://doi.org/10.3389/fnagi.2024.1498756
9. Collier, T. J., Kanaan, N. M., Kordower, J. H. (2011). Ageing as a primary risk factor for Parkinson's disease: evidence from studies of non-human primates. Nature Reviews Neuroscience, 12(6), 359-366. https://doi.org/10.1038/nrn3039
10. Hindle J. V. (2010). Ageing, neurodegeneration and Parkinson's disease. Age and ageing, 39(2), 156–161. https://doi.org/10.1093/ageing/afp223
11. Srinivasan, E., Chandrasekhar, G., Chandrasekar, P., Anbarasu, K., Vickram, A. S., Karunakaran, R., Srikumar, P. S. (2021). Alpha-synuclein aggregation in Parkinson's disease. Frontiers in medicine, 8, 736978. https://doi.org/10.3389/fmed.2021.736978
12. Campêlo, C. L. D. C., & Silva, R. H. (2017). Genetic Variants in SNCA and the Risk of Sporadic Parkinson's Disease and Clinical Outcomes: A Review. Parkinson's disease, 2017, 4318416. https://doi.org/10.1155/2017/4318416
13. Xiang H. (2025). The interplay between α-synuclein aggregation and necroptosis in Parkinson's disease: a spatiotemporal perspective. Frontiers in neuroscience, 19, 1567445. https://doi.org/10.3389/fnins.2025.1567445
14. Volpicelli-Daley, L., & Brundin, P. (2018). Prion-like propagation of pathology in Parkinson disease. Handbook of clinical neurology, 153, 321–335. https://doi.org/10.1016/B978-0-444-63945-5.00017-9
15. Mogensen, F. L. H., Delle, C., Nedergaard, M. (2021). The glymphatic system (En) during inflammation. International journal of molecular sciences, 22(14), 7491. https://doi.org/10.3390/ijms22147491
16. Chakrabarti, S. K., & Chattopadhyay, D. (2024). From immune sanctuary to neurological battlefield: the role of neuroimmune cells. Exploratory Research and Hypothesis in Medicine, 9(4), 308-327. https://doi.org/10.14218/ERHM.2024.00026
17. Subramaniam, S. R., Federoff, H. J. (2017). Targeting Microglial Activation States as a Therapeutic Avenue in Parkinson's Disease. Frontiers in aging neuroscience, 9, 176. https://doi.org/10.3389/fnagi.2017.00176
18. Chia, S. Y., Li, M., Li, Z., Tu, H., Lee, J. W. L., Qiu, L., Ling, J., Reynolds, R., Albani, S., Tan, E. K., Ng, A. S. L., Chen, J., & Zeng, L. (2025). Single-nucleus transcriptomics reveals a distinct microglial state and increased MSR1-mediated phagocytosis as common features across dementia subtypes. Genome medicine, 17(1), 92. https://doi.org/10.1186/s13073-025-01519-4
19. Roodveldt, C., Bernardino, L., Oztop-Cakmak, O., Dragic, M., Fladmark, K. E., Ertan, S., ... & Romero-Ramos, M. (2024). The immune system in Parkinson's disease: what we know so far. Brain, 147(10), 3306-3324. https://doi.org/10.1093/brain/awae177
20. Zhang, L., Dong, Y., Xu, X., & Xu, Z. (2012). The role of autophagy in Parkinson's disease. Neural regeneration research, 7(2), 141–145. https://doi.org/10.3969/j.issn.1673-5374.2012.02.011
21. Dias, V., Junn, E., & Mouradian, M. M. (2013). The role of oxidative stress in Parkinson's disease. Journal of Parkinson’s disease, 3(4), 461-491. https://doi.org/10.3233/JPD-13023
22. Menozzi, E., Macnaughtan, J., & Schapira, A. H. (2021). The gut-brain axis and Parkinson disease: clinical and pathogenetic relevance. Annals of Medicine, 53(1), 611-625. https://doi.org/10.1080/07853890.2021.1890330
23. Espinosa‐Oliva, A. M., Ruiz, R., Soto, M. S., Boza‐Serrano, A., Rodriguez‐Perez, A. I., Roca‐Ceballos, M. A., ... & de Pablos, R. M. (2024). Inflammatory bowel disease induces pathological α‐synuclein aggregation in the human gut and brain. Neuropathology and Applied Neurobiology, 50(1), e12962. https://doi.org/10.1111/nan.12962
24. Klann, E. M., Dissanayake, U., Gurrala, A., Farrer, M., Shukla, A. W., Ramirez-Zamora, A., Vedam-Mai, V. (2022). The gut–brain axis and its relation to Parkinson’s disease: a review. Frontiers in aging neuroscience, 13, 782082. https://doi.org/10.3389/fnagi.2021.782082
25. Rietdijk, C. D., Perez-Pardo, P., Garssen, J., Van Wezel, R. J., & Kraneveld, A. D. (2017). Exploring Braak’s hypothesis of Parkinson’s disease. Frontiers in neurology, 8, 37. https://doi.org/10.3389/fneur.2017.00037
26. Khalaf, N. A., Badr, M. Y., & Nasef, M. (2025). Assessment of Prodromal Gastrointestinal Manifestations in Idiopathic Parkinson's Disease. The Open Biomarkers Journal, 15(1). https://doi.org/10.2174/0118753183382955250509055110
27. Pellegrini, C., D’Antongiovanni, V., Miraglia, F., Rota, L., Benvenuti, L., Di Salvo, C., ... & Fornai, M. (2022). Enteric α-synuclein impairs intestinal epithelial barrier through caspase-1-inflammasome signaling in Parkinson’s disease before brain pathology. npj Parkinson's Disease, 8(1), 9. https://doi.org/10.1038/s41531-021-00263-x
28. Kim, J. J., Vitale, D., Otani, D. V., Lian, M. M., Heilbron, K., Iwaki, H., ... & Mata, I. (2024). Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease. Nature genetics, 56(1), 27-36. https://doi.org/10.1038/s41588-023-01584-8
29. Tönges, L., Kwon, E. H., & Klebe, S. (2022). Monogenetic Forms of Parkinson’s Disease–Bridging the Gap Between Genetics and Biomarkers. Frontiers in Aging Neuroscience, 14, 822949. https://doi.org/10.3389/fnagi.2022.822949
30. Pihlstrøm, L., Fan, C. C., Frei, O., Tan, M., Karunamuni, R. A., Blauwendraat, C., Andreassen, O. A. (2022). Genetic stratification of age‐dependent Parkinson's disease risk by polygenic hazard score. Movement disorders, 37(1), 62-69. https://doi.org/10.1002/mds.28808
31. Rosal, A. E., Martin, S. L., Strafella, A. P. (2025). The role of Apolipoprotein E4 on cognitive impairment in Parkinson’s disease and Parkinsonisms. Frontiers in Neuroscience, 19, 1515374. https://doi.org/10.3389/fnins.2025.1515374
32. Beheshti, I. (2025). Risk and Protective Factors in Parkinsons Disease. arXiv preprint arXiv:2503.07798. https://doi.org/10.48550/arXiv.2503.07798
33. Grossauer, A., Hemicker, G., Krismer, F., Peball, M., Djamshidian, A., Poewe, W., Heim, B. (2023). α‐Synuclein seed amplification assays in the diagnosis of synucleinopathies using cerebrospinal fluid—a systematic review and meta‐analysis. Movement disorders clinical practice, 10(5), 737-747. https://doi.org/10.1002/mdc3.13710
34. Gibbons, C. H., Levine, T., Adler, C., Bellaire, B., Wang, N., Stohl, J., Agarwal, P., Aldridge, G. M., Barboi, A., Evidente, V. G. H., Galasko, D., Geschwind, M. D., Gonzalez-Duarte, A., Gil, R., Gudesblatt, M., Isaacson, S. H., Kaufmann, H., Khemani, P., Kumar, R., Lamotte, G., Freeman, R. (2024). Skin Biopsy Detection of Phosphorylated α-Synuclein in Patients With Synucleinopathies. JAMA, 331(15), 1298–1306. https://doi.org/10.1001/jama.2024.0792
35. Brockmann, K., Lerche, S., Baiardi, S., Rossi, M., Wurster, I., Quadalti, C., Roeben, B., Mammana, A., Zimmermann, M., Hauser, A. K., Deuschle, C., Schulte, C., Liepelt-Scarfone, I., Gasser, T., Parchi, P. (2024). CSF α-synuclein seed amplification kinetic profiles are associated with cognitive decline in Parkinson's disease. NPJ Parkinson's disease, 10(1), 24. https://doi.org/10.1038/s41531-023-00627-5
36. Gao, S., Wang, Z., Huang, Y., Yang, G., Wang, Y., Yi, Y., ... & Li, J. (2025). Early detection of Parkinson’s disease through multiplex blood and urine biomarkers prior to clinical diagnosis. npj Parkinson's Disease, 11(1), 35. https://doi.org/10.1038/s41531-025-00888-2
37. Hällqvist, J., Bartl, M., Dakna, M., Schade, S., Garagnani, P., Bacalini, M. G., Mollenhauer, B. (2024). Plasma proteomics identify biomarkers predicting Parkinson’s disease up to 7 years before symptom onset. Nature communications, 15(1), 4759. https://doi.org/10.1038/s41467-024-48961-3
38. Tönges, L., Buhmann, C., Klebe, S., Klucken, J., Kwon, E. H., Müller, T., Pedrosa, D. J., Schröter, N., Riederer, P., Lingor, P. (2022). Blood-based biomarker in Parkinson's disease: potential for future applications in clinical research and practice. Journal of neural transmission (Vienna, Austria : 1996), 129(9), 1201–1217. https://doi.org/10.1007/s00702-022-02498-1
39. Diaz-Ortiz, M. E., Seo, Y., Posavi, M., Carceles Cordon, M., Clark, E., Jain, N., Charan, R., Gallagher, M. D., Unger, T. L., Amari, N., Skrinak, R. T., Davila-Rivera, R., Brody, E. M., Han, N., Zack, R., Van Deerlin, V. M., Tropea, T. F., Luk, K. C., Lee, E. B., Weintraub, D., Chen-Plotkin, A. S. (2022). GPNMB confers risk for Parkinson's disease through interaction with α-synuclein. Science (New York, N.Y.), 377(6608), eabk0637. https://doi.org/10.1126/science.abk0637
40. Richardson, A., Kundu, A., Henao, R., Lee, T., Scott, B. L., Grewal, D. S., Fekrat, S. (2024). Multimodal Retinal Imaging Classification for Parkinson's Disease Using a Convolutional Neural Network. Translational vision science & technology, 13(8), 23. https://doi.org/10.1167/tvst.13.8.23
41. Mancini, M., Afshari, M., Almeida, Q., Amundsen-Huffmaster, S., Balfany, K., Camicioli, R., Christiansen, C., Dale, M. L., Dibble, L. E., Earhart, G. M., Ellis, T. D., Griffith, G. J., Hackney, M. E., Hopkins, J., Horak, F. B., Jones, K. E., Ling, L., O'Keefe, J. A., Kwei, K., Olivier, G., Corcos, D. M. (2025). Digital gait biomarkers in Parkinson's disease: susceptibility/risk, progression, response to exercise, and prognosis. NPJ Parkinson's disease, 11(1), 51. https://doi.org/10.1038/s41531-025-00897-1
42. Yang, Y., Hu, L., Chen, Y., Gu, W., Lin, G., Xie, Y., & Nie, S. (2025). Identification of Parkinson's disease using MRI and genetic data from the PPMI cohort: an improved machine learning fusion approach. Frontiers in aging neuroscience, 17, 1510192. https://doi.org/10.3389/fnagi.2025.1510192
43. Huang, Y., Liao, J., Liu, X., Zhong, Y., Cai, X., & Long, L. (2021). Review: The Role of Intestinal Dysbiosis in Parkinson's Disease. Frontiers in cellular and infection microbiology, 11, 615075. https://doi.org/10.3389/fcimb.2021.615075
44. Guo, M., Gao, H., Wang, Y., & Xiang, Y. (2025). Exploring the role of gut microbiota in Parkinson's disease: insights from fecal microbiota transplantation. Frontiers in neuroscience, 19, 1574512. https://doi.org/10.3389/fnins.2025.1574512
45. Chen, K., Sun, L., Liu, Y., Chen, R. (2025). Safety and efficacy of fecal microbiota transplantation in the treatment of Parkinson's disease: a systematic review of clinical trials. Frontiers in neuroscience, 19, 1639911. https://doi.org/10.3389/fnins.2025.1639911
46. Freitas, M. E., & Fox, S. H. (2016). Nondopaminergic treatments for Parkinson's disease: current and future prospects. Neurodegenerative disease management, 6(3), 249–268. https://doi.org/10.2217/nmt-2016-0005
47. Sharma, V. D., Patel, M., & Miocinovic, S. (2020). Surgical Treatment of Parkinson's Disease: Devices and Lesion Approaches. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 17(4), 1525–1538. https://doi.org/10.1007/s13311-020-00939-x
48. Xiao, B., Tan, E. K. (2025). Prasinezumab slows motor progression in Parkinsons disease: beyond the clinical data. NPJ Parkinson's disease, 11(1), 31. https://doi.org/10.1038/s41531-025-00886-4
49. Fields, C. R., Bengoa-Vergniory, N., & Wade-Martins, R. (2019). Targeting Alpha-Synuclein as a Therapy for Parkinson's Disease. Frontiers in molecular neuroscience, 12, 299. https://doi.org/10.3389/fnmol.2019.00299
50. Alfaidi, M., Barker, R. A., Kuan, W. L. (2024). An update on immune-based alpha-synuclein trials in Parkinson's disease. Journal of neurology, 272(1), 21. https://doi.org/10.1007/s00415-024-12770-x
51. Lv, D., Feng, P., Guan, X., Liu, Z., Li, D., Xue, C., Bai, B., Hölscher, C. (2024). Neuroprotective effects of GLP-1 class drugs in Parkinson's disease. Frontiers in neurology, 15, 1462240. https://doi.org/10.3389/fneur.2024.1462240
52. Meissner, W. G., Remy, P., Giordana, C., Maltête, D., Derkinderen, P., Houéto, J. L., Rascol, O. (2024). Trial of lixisenatide in early Parkinson’s disease. New England journal of medicine, 390(13), 1176-1185. https://doi.org/10.1056/NEJMoa2312323
53. Gamborg, M., Grand, M. K., Arvedsen, J., Meaidi, A., & Mørch, L. S. (2025). GLP-1 Agonists as Potential Neuromodulators in Development of Parkinson's Disease: A Nationwide Cohort Study. European journal of neurology, 32(2), e70075. https://doi.org/10.1111/ene.70075
54. AI speeds up drug design for Parkinson’s ten-fold. Nature Chemical Biology. Website. [Cited 25 August 2025] Available from URL: https://www.cam.ac.uk/research/news/ai-speeds-up-drug-design-for-parkinsons-ten-fold
55. Alterity Therapeutics Announces Successful Completion of Phase 1 Clinical Trial of PBT434. . Website. [Cited 25 August 2025] Available from URL:https://alteritytherapeutics.com/investor-centre/news/2019/07/29/alterity-therapeutics-announces-successful-completion-of-phase-1-clinical-trial/
56. Tabar, V., Sarva, H., Lozano, A. M., Fasano, A., Kalia, S. K., Yu, K. K. H., Brennan, C., Ma, Y., Peng, S., Eidelberg, D., Tomishima, M., Irion, S., Stemple, W., Abid, N., Lampron, A., Studer, L., & Henchcliffe, C. (2025). Phase I trial of hES cell-derived dopaminergic neurons for Parkinson's disease. Nature, 641(8064), 978–983. https://doi.org/10.1038/s41586-025-08845-y
57. Sawamoto, N., Doi, D., Nakanishi, E., Sawamura, M., Kikuchi, T., Yamakado, H., Taruno, Y., Shima, A., Fushimi, Y., Okada, T., Kikuchi, T., Morizane, A., Hiramatsu, S., Anazawa, T., Shindo, T., Ueno, K., Morita, S., Arakawa, Y., Nakamoto, Y., Miyamoto, S., … Takahashi, J. (2025). Phase I/II trial of iPS-cell-derived dopaminergic cells for Parkinson's disease. Nature, 641(8064), 971–977. https://doi.org/10.1038/s41586-025-08700-0
58. Clark, B. J., Lelos, M. J., Loring, J. F. (2024). Advancing Parkinson's disease treatment: cell replacement therapy with neurons derived from pluripotent stem cells. Stem cells (Dayton, Ohio), 42(9), 781–790. https://doi.org/10.1093/stmcls/sxae042
59. Shalaby, K. E., & El-Agnaf, O. M. A. (2022). Gene-Based Therapeutics for Parkinson's Disease. Biomedicines, 10(8), 1790. https://doi.org/10.3390/biomedicines10081790
60. Yang, Y., Yuan, Y., Zhang, G., Wang, H., Chen, Y. C., Liu, Y., Tarolli, C. G., Crepeau, D., Bukartyk, J., Junna, M. R., Videnovic, A., Ellis, T. D., Lipford, M. C., Dorsey, R., & Katabi, D. (2022). Artificial intelligence-enabled detection and assessment of Parkinson's disease using nocturnal breathing signals. Nature medicine, 28(10), 2207–2215. https://doi.org/10.1038/s41591-022-01932-x
61. Hall, A., Bandres-Ciga, S., Diez-Fairen, M., Quinn, J. P., & Billingsley, K. J. (2020). Genetic Risk Profiling in Parkinson's Disease and Utilizing Genetics to Gain Insight into Disease-Related Biological Pathways. International journal of molecular sciences, 21(19), 7332. https://doi.org/10.3390/ijms21197332
62. Crotty, G. F., Keavney, J. L., Alcalay, R. N., Marek, K., Marshall, G. A., Rosas, H. D., Schwarzschild, M. A. (2022). Planning for Prevention of Parkinson Disease: Now Is the Time. Neurology, 99(7 Suppl 1), 1–9. https://doi.org/10.1212/WNL.0000000000200789
63. Gao, S., Wang, Z., Huang, Y., Yang, G., Wang, Y., Yi, Y., Zhou, Q., Jian, X., Zhao, G., Li, B., Xu, L., Xia, K., Tang, B., & Li, J. (2025). Early detection of Parkinson's disease through multiplex blood and urine biomarkers prior to clinical diagnosis. NPJ Parkinson's disease, 11(1), 35. https://doi.org/10.1038/s41531-025-00888-2
64. Soman, K., Nelson, C. A., Cerono, G., Goldman, S. M., Baranzini, S. E., Brown, E. G. (2023). Early detection of Parkinson's disease through enriching the electronic health record using a biomedical knowledge graph. Frontiers in medicine, 10, 1081087. https://doi.org/10.3389/fmed.2023.1081087
65. Mahlknecht, P., & Poewe, W. (2024). Pharmacotherapy for Disease Modification in Early Parkinson's Disease: How Early Should We Be?. Journal of Parkinson's disease, 14(s2), S407–S421. https://doi.org/10.3233/JPD-230354
66. Adrissi, J., & Fleisher, J. (2022). Moving the Dial Toward Equity in Parkinson's Disease Clinical Research: a Review of Current Literature and Future Directions in Diversifying PD Clinical Trial Participation. Current neurology and neuroscience reports, 22(8), 475–483. https://doi.org/10.1007/s11910-022-01212-8
