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Minocycline in neurological disorders treatment
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Minociclina, uma tetraciclina semissintética de segunda geração que tem demonstrado, à parte de sua atividade bacteriostática através de bloqueio da síntese de proteínas, potente ação anti-inflamatória que permitiu sua utilização aprovada pela Food and Drug Administration para tratamento de Artrite Reumatoide, entre outras doenças com intenso componente inflamatório. No final dos anos 90, após a descobertada caspase-1 e sua relação com a apoptose, e por outro lado, o perfil neurofarmacocinético único da minociclina (que permite alta e rápida concentração do composto no SNS) as pesquisas no papel neuroprotetor deste fármaco se intensificaram. Durante este século extensa bibliografia mundial tem demonstrado sua ação anti-neuroinflamatória, imunomoduladora e antiapoptótica em patologias do cérebro e medula espinhal. Doenças agudas como Lesão Cerebral por trauma e/ou Hemorragia, Hipóxia e Lesão Medular Aguda, assim como doenças neurodegenerativas crónicas, principalmente Alzheimer, Parkinson, Huntington, Esclerose Lateral Amiotrófica, Doenças do Príon e Esclerose Múltipla partilham, obviamente com tempo de evolução distintos, intenso e irrefreável processo inflamatório com super-ativação da resposta imunológica que ocasiona massiva neuroapoptose com alta letalidade. Ao longo da revisão, foram observados avanços impressionantes nos intricados mecanismos moleculares e celulares envolvidos na fisiopatologia dessas doenças, bem como as ações terapêuticas, através de diversos caminhos, da minociclina. Foi revisada também, a possível utilização da droga como adjuvante no tratamento onconeurológico e nas patologias psiquiátricas à luz dos novos conceitos, envolvendo os frustrantes resultados na terapêutica ao longo dos anos.
Como seria de esperar, estudos importantes contradizem essas expectativas, com resultados ineficazes e até deletérios do uso da minociclina com o papel neuroprotetor e serão abordados neste trabalho. Estudos importantes de alto nível demonstram resultados ineficazes e até deletérios com o uso da minociclina como agente neuroprotetor, contradizendo os dados benéficos. Tais eventos mostram que o papel da minociclina na neurologia está longe de ser consenso geral.
Minocycline, a semi-synthetic, second generation tetracycline, has demonstrated, aside its blocking protein synthesis bacteriostatic action, a potent anti-inflammatory effect that allowed the drug to be approved by Food and Drug Administration for rheumatoid arthritis among other disorders with an intense inflammatory feature. By the end of the 1990`s, after the discovery of caspase-1 (previously interleukin-1ß converting enzyme), and its relation with apoptosis and, on the other hand the unique profile of minocycline (rapid and high central nervous system concentration after administration), the research about this compound as a neuroprotectant has been intensified. During the current century, wide-world bibliography has been showing minocycline`s anti-neuroinflammatory, immunomodulatory and antiapoptotic features, in brain and spinal cord disorders. Acute diseases such as traumatic and/or hemorrhagic or hypoxic brain injury and spinal cord injury as well as neurodegenerative chronic diseases, mainly Alzheimer’s Disease, Parkinson’s Disease, Huntington Disease, amyotrophic lateral sclerosis, prion diseases and multiple sclerosis share, obviously with different progression timing, intense and unstoppable inflammatory process with oversized immunologic response that lead to massive neuronal apoptosis and lethality. Throughout the revision it was observed an impressive breakthrough in the intricate molecular and cellular mechanisms in the pathophysiology of these diseases and the target therapeutic effects of minocycline through diverse pathways. Moreover, we updated the possible use of the antibiotic as an adjuvant in neuro-oncologic treatment and psychiatric disorders, according to new concepts, trying to improve the poor successful outcome. Important high-level studies demonstrate ineffective and even deleterious results with the use of minocycline as a neuroprotective agent, contradicting the beneficial data. Such events show that the role of minocycline in neurology is far from general consensus.
Minocycline, a semi-synthetic, second generation tetracycline, has demonstrated, aside its blocking protein synthesis bacteriostatic action, a potent anti-inflammatory effect that allowed the drug to be approved by Food and Drug Administration for rheumatoid arthritis among other disorders with an intense inflammatory feature. By the end of the 1990`s, after the discovery of caspase-1 (previously interleukin-1ß converting enzyme), and its relation with apoptosis and, on the other hand the unique profile of minocycline (rapid and high central nervous system concentration after administration), the research about this compound as a neuroprotectant has been intensified. During the current century, wide-world bibliography has been showing minocycline`s anti-neuroinflammatory, immunomodulatory and antiapoptotic features, in brain and spinal cord disorders. Acute diseases such as traumatic and/or hemorrhagic or hypoxic brain injury and spinal cord injury as well as neurodegenerative chronic diseases, mainly Alzheimer’s Disease, Parkinson’s Disease, Huntington Disease, amyotrophic lateral sclerosis, prion diseases and multiple sclerosis share, obviously with different progression timing, intense and unstoppable inflammatory process with oversized immunologic response that lead to massive neuronal apoptosis and lethality. Throughout the revision it was observed an impressive breakthrough in the intricate molecular and cellular mechanisms in the pathophysiology of these diseases and the target therapeutic effects of minocycline through diverse pathways. Moreover, we updated the possible use of the antibiotic as an adjuvant in neuro-oncologic treatment and psychiatric disorders, according to new concepts, trying to improve the poor successful outcome. Important high-level studies demonstrate ineffective and even deleterious results with the use of minocycline as a neuroprotective agent, contradicting the beneficial data. Such events show that the role of minocycline in neurology is far from general consensus.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2021, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Minocycline Antiinflammation Antiapoptotic Immunomodulation and neuroprotection Mestrado integrado - 2021