Doxiciclina como potencial terapêutico na doença de Parkinson

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Publicado May 6, 2025
DOI https://doi.org/10.25248/reas.e20218.2025

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Leon Claudio Pinheiro Leal
Universidade Federal do Pará
Lais Russo Resque Pedrosa
Universidade de Aarhus
José Augusto Pereira Carneiro Muniz
Centro Nacional de Primatas/ Instituto Evandro Chagas
Lane Viana Krejcová
Universidade Federal do Pará
Bruno Duarte Gomes
Universidade Federal do Pará

Resumo

Objetivo: Analisar as evidências disponíveis sobre o uso da doxiciclina (DOX) como potencial agente terapêutico na Doença de Parkinson (DP), considerando seus efeitos neuroprotetores e anti-inflamatórios. Revisão bibliográfica: A DP é caracterizada pela degeneração progressiva dos neurônios dopaminérgicos, levando a sintomas motores e não motores debilitantes. Estudos indicam que a neuroinflamação tem papel crucial na progressão da doença, tornando-se um alvo terapêutico promissor. A DOX, uma tetraciclina de segunda geração, apresenta propriedades anti-inflamatórias e neuroprotetoras, além de alta lipossolubilidade e capacidade de atravessar a barreira hematoencefálica. Modelos experimentais demonstraram que a DOX reduz a degeneração neuronal, inibe a ativação da micróglia e modula a agregação de α-sinucleína, proteína associada à patogênese da DP. Esses achados sugerem que a DOX pode retardar a progressão da doença e reduzir sintomas motores e neuro inflamatórios. Considerações finais: A DOX se mostra um candidato promissor para a neuroproteção dopaminérgica, mas estudos clínicos são necessários para validar sua eficácia na DP. A reorientação desse antibiótico pode representar uma nova estratégia terapêutica para doenças neurodegenerativas.

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Como Citar
LealL. C. P., PedrosaL. R. R., MunizJ. A. P. C., KrejcováL. V., & GomesB. D. (2025). Doxiciclina como potencial terapêutico na doença de Parkinson. Revista Eletrônica Acervo Saúde, 25(5), e20218. https://doi.org/10.25248/reas.e20218.2025
Edição
v. 25 n. 5 (2025): Revista Eletrônica Acervo Saúde (ISSN 2178-2091) | Volume 25 (5) | 2025
Seção
Revisão Bibliográfica

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Referências

1. AGWUH KN, MACGOWAN A. Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. Journal of Antimicrobial Chemotherapy, 2006, 58(2): 256-265.

2. ASCHERIO A, SCHWARZSCHILD MA. The epidemiology of Parkinson’s disease: Risk factors and prevention. The Lancet Neurology, 2016, 15: 1156-1168.

3. BAUSO DJ, et al. Incidence and prevalence of Parkinson’s disease in Buenos Aires City, Argentina. European Journal of Neurology, 2012, 19(8): 1108-1113.

4. BJØRKLUND G, et al. Preventive treatments to slow substantia nigra damage and Parkinson’s disease progression: A critical perspective review. Pharmacological Research, 2020, 161: 105065.

5. BLANDINI F, et al. Functional changes of the basal ganglia circuitry in Parkinson's disease. Progress in Neurobiology, 2020, 62(1): 63-88.

6. BORTOLANZA M, et al. Tetracycline repurposing in neurodegeneration: Focus on Parkinson’s disease. Journal of Neural Transmission, 2018, 125: 1403-1415.

7. BOVOLENTA TM, et al. Average annual cost of Parkinson’s disease in São Paulo, Brazil, with a focus on disease-related motor symptoms. Clinical Interventions in Aging, 2017, 2095-2108.

8. BRAAK H, DEL TREDICI K. Cortico-basal ganglia-cortical circuitry in Parkinson's disease reconsidered. Experimental Neurology, 2008, 212(1): 226-229.

9. CHOPRA I, ROBERTS M. Tetracycline antibiotics: Mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiology and Molecular Biology Reviews, 2001, 65(2): 232-260.

10. CUNHA MB. Metodologias para estudo dos usuários de informação científica e tecnológica. Revista de Biblioteconomia de Brasília, 1982, 10(2): 5-19.

11. DE VIRGILIO A, et al. Parkinson’s disease: Autoimmunity and neuroinflammation. Autoimmunity Reviews, 2016, 15: 1005–1011.

12. DEL ROSSO JQ. Oral doxycycline in the management of acne vulgaris: Current perspectives on clinical use and recent findings with a new double-scored small tablet formulation. The Journal of Clinical and Aesthetic Dermatology, 2015, 8(5): 19.

13. DOMINGO A, KLEIN C. Genetics of Parkinson disease. In: HANDBOOK OF CLINICAL NEUROLOGY, 2018.

14. ELSWORTH JD. Parkinson’s disease treatment: Past, present, and future. Journal of Neural Transmission, 2020, 127(5): 785-791.

15. FABRE J, et al. Distribution and excretion of doxycycline in man. Chemotherapy, 1966, 11(2): 73-85.

16. FRANKLIN TJ, et al. The bacterial cell wall—A vulnerable shield. In: Biochemistry of Antimicrobial Action, 1975. p. 22-55.

17. GELPI E, et al. Multiple organ involvement by alpha-synuclein pathology in Lewy body disorders. Movement Disorders, 2014, 29(8): 1010–1018.

18. GIRGENRATH M, et al. Pathology is alleviated by doxycycline in a laminin‐α2–null model of congenital muscular dystrophy. Annals of Neurology, 2009, 65(1): 47-56.

19. GUSTAVSSON A, et al. Cost of disorders of the brain in Europe 2010. European Neuropsychopharmacology, 2011, 21(10): 718-779.

20. HONG Z, et al. DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease. Brain, 2010, 133: 713–726.

21. JANKOVIC J. Parkinson’s disease: Clinical features and diagnosis. Journal of Neurology, Neurosurgery & Psychiatry, 2018, 79(4): 368–376.

22. KALIA LV, LANG AE. Parkinson's disease. The Lancet, 2015, 386(9996): 896-912.

23. LIU TW, et al. Biomarker of neuroinflammation in Parkinson’s disease. International Journal of Molecular Sciences, 2022, 23(8): 4148.

24. MCGREGOR MM, NELSON AB. Circuit mechanisms of Parkinson’s disease. Neuron, 2019, 101(6): 1042-1056.

25. MOLLENHAUER B, et al. Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls. Neurology, 2017, 89: 1959–1969.

26. MOREJÓN GM, et al. Actualización en tetraciclinas. Revista Cubana de Farmacia, 2003, 37(3): 1.

27. NAU R, et al. Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections. Clinical Microbiology Reviews, 2010, 23(4): 858-883.

28. PALDINO E, et al. Neuroprotective effects of doxycycline in the R6/2 mouse model of Huntington's disease. Neurobiology of Disease, 2017, 105: 152-163.

29. PONT-SUNYER C, et al. The onset of nonmotor symptoms in Parkinson’s disease (the ONSET PD study). Movement Disorders, 2015, 30(2): 229–237.

30. SANTA-CECÍLIA FV, et al. Doxycycline suppresses microglial activation by inhibiting the p38 MAPK and NF-kB signaling pathways. Neurotoxicity Research, 2016, 29: 447-459.

31. SANTOS-LOBATO BL, et al. Doxycycline to treat levodopa-induced dyskinesias in Parkinson’s disease: A preliminary study. Arquivos de Neuro-Psiquiatria, 2023, 81(5): 460-468.

32. TANSEY MG, GOLDBERG MS. Neuroinflammation in Parkinson's disease: Its role in neuronal death and implications for therapeutic intervention. Neurobiology of Disease, 2010, 37(3): 510-518.

33. THOMAS M, et al. Minocycline and other tetracycline derivatives: A neuroprotective strategy in Parkinson's disease and Huntington's disease. Clinical Neuropharmacology, 2003, 26(1): 18-23.

34. TOLOSA E, et al. Challenges in the diagnosis of Parkinson's disease. The Lancet Neurology, 2021, 20(5): 385-397.

35. TYSNES OB, STORSTEIN A. Epidemiology of Parkinson’s disease. Journal of Neural Transmission, 2017, 124: 901-905.

36. VON CAMPENHAUSEN S, et al. Prevalence and incidence of Parkinson's disease in Europe. European Neuropsychopharmacology, 2005, 15(4): 473-490.