Palabras clave
Doxiciclina
Tratamiento Farmacológico
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Resumen
Objetivo: Analizar la evidencia disponible sobre el uso de la doxiciclina (DOX) como un posible agente terapéutico en la Enfermedad de Parkinson (EP), considerando sus efectos neuroprotectores y antiinflamatorios. Revisión bibliográfica: La EP se caracteriza por la degeneración progresiva de las neuronas dopaminérgicas, lo que provoca síntomas motores y no motores debilitantes. Estudios indican que la neuroinflamación desempeña un papel crucial en la progresión de la enfermedad, convirtiéndola en un objetivo terapéutico prometedor. La DOX, una tetraciclina de segunda generación, posee propiedades antiinflamatorias y neuroprotectoras, además de alta liposolubilidad y capacidad para atravesar la barrera hematoencefálica. Modelos experimentales han demostrado que la DOX reduce la degeneración neuronal, inhibe la activación de la microglía y modula la agregación de α-sinucleína, una proteína asociada a la patogénesis de la EP. Estos hallazgos sugieren que la DOX podría ralentizar la progresión de la enfermedad y aliviar los síntomas motores y neuroinflamatorios. Consideraciones finales: La DOX se presenta como un candidato prometedor para la neuroprotección dopaminérgica, pero se requieren estudios clínicos para validar su eficacia en la EP. La reutilización de este antibiótico podría representar una nueva estrategia terapéutica para enfermedades neurodegenerativas.
Referencias
AGWUH KN, MACGOWAN A. Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. Journal of Antimicrobial Chemotherapy, 2006, 58(2): 256-265.
ASCHERIO A, SCHWARZSCHILD MA. The epidemiology of Parkinson’s disease: Risk factors and prevention. The Lancet Neurology, 2016, 15: 1156-1168.
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.
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.
BLANDINI F, et al. Functional changes of the basal ganglia circuitry in Parkinson's disease. Progress in Neurobiology, 2020, 62(1): 63-88.
BORTOLANZA M, et al. Tetracycline repurposing in neurodegeneration: Focus on Parkinson’s disease. Journal of Neural Transmission, 2018, 125: 1403-1415.
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.
BRAAK H, DEL TREDICI K. Cortico-basal ganglia-cortical circuitry in Parkinson's disease reconsidered. Experimental Neurology, 2008, 212(1): 226-229.
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.
CUNHA MB. Metodologias para estudo dos usuários de informação científica e tecnológica. Revista de Biblioteconomia de Brasília, 1982, 10(2): 5-19.
DE VIRGILIO A, et al. Parkinson’s disease: Autoimmunity and neuroinflammation. Autoimmunity Reviews, 2016, 15: 1005–1011.
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.
DOMINGO A, KLEIN C. Genetics of Parkinson disease. In: HANDBOOK OF CLINICAL NEUROLOGY, 2018.
ELSWORTH JD. Parkinson’s disease treatment: Past, present, and future. Journal of Neural Transmission, 2020, 127(5): 785-791.
FABRE J, et al. Distribution and excretion of doxycycline in man. Chemotherapy, 1966, 11(2): 73-85.
FRANKLIN TJ, et al. The bacterial cell wall—A vulnerable shield. In: Biochemistry of Antimicrobial Action, 1975. p. 22-55.
GELPI E, et al. Multiple organ involvement by alpha-synuclein pathology in Lewy body disorders. Movement Disorders, 2014, 29(8): 1010–1018.
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.
GUSTAVSSON A, et al. Cost of disorders of the brain in Europe 2010. European Neuropsychopharmacology, 2011, 21(10): 718-779.
HONG Z, et al. DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease. Brain, 2010, 133: 713–726.
JANKOVIC J. Parkinson’s disease: Clinical features and diagnosis. Journal of Neurology, Neurosurgery & Psychiatry, 2018, 79(4): 368–376.
KALIA LV, LANG AE. Parkinson's disease. The Lancet, 2015, 386(9996): 896-912.
LIU TW, et al. Biomarker of neuroinflammation in Parkinson’s disease. International Journal of Molecular Sciences, 2022, 23(8): 4148.
MCGREGOR MM, NELSON AB. Circuit mechanisms of Parkinson’s disease. Neuron, 2019, 101(6): 1042-1056.
MOLLENHAUER B, et al. Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls. Neurology, 2017, 89: 1959–1969.
MOREJÓN GM, et al. Actualización en tetraciclinas. Revista Cubana de Farmacia, 2003, 37(3): 1.
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.
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.
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.
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.
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.
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.
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.
TOLOSA E, et al. Challenges in the diagnosis of Parkinson's disease. The Lancet Neurology, 2021, 20(5): 385-397.
TYSNES OB, STORSTEIN A. Epidemiology of Parkinson’s disease. Journal of Neural Transmission, 2017, 124: 901-905.
VON CAMPENHAUSEN S, et al. Prevalence and incidence of Parkinson's disease in Europe. European Neuropsychopharmacology, 2005, 15(4): 473-490.