ABSTRACT
Introducción: La enfermedad de Alzheimer (EA) es una compleja enfermedad neurodegenerativa caracterizada por inflamación, neurotoxicidad, estrés oxidativo y gliosis reactiva. La microglía y los astrocitos no solo actúan como células presentadoras de antígenos, sino que constituyen células efectoras, liberando moléculas proinflamatorias que promueven la excitotoxicidad y la neurodegeneración. Objetivo: En la presente revisión bibliográfica se discute el papel de la glía, específicamente de la microglía y el astrocito en la fisiopatología de la EA y las posibles implicaciones terapéuticas. Desarrollo: La emergente evidencia del papel patogénico y la activación de vías de inflamación a partir de la microglía y el astrocito, los factores neurotóxicos liberados por estas células cuando están activadas, y cómo estos pueden desestabilizar la homeostasis del sistema nervioso central, sostienen la idea de que la inflamación inducida por la glía amplifica la EA. Conclusiones: La inhibición de la inflamación por inactivación de la glía, pudiera reducir la producción de factores que contribuyen con la toxicidad, resultando ser un beneficio clínico. La microglía y el astrocito constituyen blancos terapéuticos en el desarrollo de nuevos fármacos para combatir esta enfermedad. Estrategias terapéuticas diseñadas para contrarrestar el efecto perjudicial de la sobreactivación de estas poblaciones celulares deben ser investigadas
Introduction: Alzheimer (AD) disease is a complex neurodegenerative disease characterised by inflammation, neurotoxicity, oxidative stress, and reactive gliosis. Microglia and astrocytes not only act as antigen-presenting cells, but also function as effector cells releasing pro-inflammatory molecules that promote excitotoxicity and neurodegeneration Objective: In the present review we discuss the role of glia, specifically microglia and astrocytes, in the pathophysiology of AD and possible therapeutic implications. Development: The growing body of evidence suggesting that microglia and astrocytes play a pathogenic role and activate inflammation pathways, the neurotoxic factors released by these cells when activated, and the way these factors may disrupt the homeostasis of the central nervous system all support the hypothesis that glia-induced inflammation exacerbates AD. Conclusions: Inhibiting inflammation by deactivating glial cells may reduce the production of factors which contribute to neurotoxicity, and therefore result in clinical improvement. Microglia and astrocytes are therapeutic targets for the development of new drugs to combat this disease. Therapeutic strategies designed to counter the detrimental effects of overactivation of these cell populations should be investigated
Subject(s)
Humans , Alzheimer Disease/physiopathology , Neuroglia/physiology , Microglia/physiology , Astrocytes/physiology , Neurogenesis/physiology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic useABSTRACT
INTRODUCTION: Alzheimer (AD) disease is a complex neurodegenerative disease characterised by inflammation, neurotoxicity, oxidative stress, and reactive gliosis. Microglia and astrocytes not only act as antigen-presenting cells, but also function as effector cells releasing pro-inflammatory molecules that promote excitotoxicity and neurodegeneration. OBJECTIVE: In the present review we discuss the role of glia, specifically microglia and astrocytes, in the pathophysiology of AD and possible therapeutic implications. DEVELOPMENT: The growing body of evidence suggesting that microglia and astrocytes play a pathogenic role and activate inflammation pathways, the neurotoxic factors released by these cells when activated, and the way these factors may disrupt the homeostasis of the central nervous system all support the hypothesis that glia-induced inflammation exacerbates AD. CONCLUSIONS: Inhibiting inflammation by deactivating glial cells may reduce the production of factors which contribute to neurotoxicity, and therefore result in clinical improvement. Microglia and astrocytes are therapeutic targets for the development of new drugs to combat this disease. Therapeutic strategies designed to counter the detrimental effects of overactivation of these cell populations should be investigated.
