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Microglia depletion as a therapeutic strategy:friend or foe in multiple sclerosis models?

Neural Regeneration Research 2023年第2期18卷 267-272页

作者： Victoria Sofia Berenice Wies Mancini Anabella Ayelen Di Pietro Laura Andrea Pasquini Universidad de Buenos Aires Facultad de Farmacia y BioquímicaDepartamento de Química BiológicaCátedra de Química Biológica PatológicaBuenos AiresArgentina Universidad de Buenos Aires Consejo Nacional de Investigaciones Científicas y TécnicasInstituto de Química y Fisicoquímica Biológicas Prof.Dr.Alejandro C.PaladiniFacultad de Farmacia y BioquímicaBuenos AiresArgentina

M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa *** activation of microglia and astrocytes is a key player in multiple sclerosis immunopathology,playing specific roles associated with anatomical location and phase of the disease and controlling demyelination and *** though reactive mic roglia can damage tissue and heighten deleterious effects and neurodegeneration,activated microglia also perform neuroprotective functions such as debris phagocytosis and growth fa ctor *** can be activated into pro-inflammato ry phenotype A1 through a mechanism mediated by activated neuroinflammatory microglia,which could also mediate *** A1 phenotype inhibits oligodendrocyte prolife ration and differe ntiation and is toxic to both oligodendrocytes and *** r,astroglial activation into phenotype A2 may also take place in response to neurodegeneration and as a protective mechanism.A variety of animal models mimicking specific multiple sclerosis features and the associated pathophysiological processes have helped establish the cascades of events that lead to the initiation,progression,and resolution of the *** colonystimulating facto r-1 receptor is expressed by myeloid lineage cells such as peripheral monocytes and macrophages and central nervous system ***,as microglia development and survival critically rely on colony-stimulating factor-1 receptor signaling,colony-stimulating factor-1 receptor inhibition can almost completely eliminate microglia from the *** this context,the present review discusses the impact of microglial depletion through colo ny-stimulating factor-1 receptor inhibition on demyelination,neurodegeneration,astroglial activation,and behavior in different multiple sclerosis models,highlighting the diversity of micr

关键词： astrocytes colony-stimulating factor-1 receptor inhibition cuprizone demyelnation microglia multiple sclerosis neurodegeneration

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