中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (2): 267-272.doi: 10.4103/1673-5374.346538

• 综述:退行性病与再生 • 上一篇    下一篇

小胶质细胞耗竭作为一种治疗策略:多发性硬化模型中的朋友还是敌人?

  

  • 出版日期:2023-02-15 发布日期:2022-08-05

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

Victoria Sofia Berenice Wies Mancini1, 2, #, Anabella Ayelen Di Pietro1, 2, #, Laura Andrea Pasquini1, 2, *   

  1. 1Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Biológica, Cátedra de Química Biológica Patológica, Buenos Aires, Argentina; 2Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro C. Paladini, Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina
  • Online:2023-02-15 Published:2022-08-05
  • Contact: Laura Andrea Pasquini, PhD, laupasq@yahoo.com.

摘要: https://orcid.org/0000-0003-4292-3463 (Laura Andrea Pasquini) 

Abstract: Multiple sclerosis is a chronic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation, genetic predisposition, and environmental factors. The 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 neurodegeneration. Even though reactive microglia can damage tissue and heighten deleterious effects and neurodegeneration, activated microglia also perform neuroprotective functions such as debris phagocytosis and growth factor secretion. Astrocytes can be activated into pro-inflammatory phenotype A1 through a mechanism mediated by activated neuroinflammatory microglia, which could also mediate neurodegeneration. This A1 phenotype inhibits oligodendrocyte proliferation and differentiation and is toxic to both oligodendrocytes and neurons. However, 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 disease. The colony-stimulating factor-1 receptor is expressed by myeloid lineage cells such as peripheral monocytes and macrophages and central nervous system microglia. Importantly, 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 brain. In this context, the present review discusses the impact of microglial depletion through colony-stimulating factor-1 receptor inhibition on demyelination, neurodegeneration, astroglial activation, and behavior in different multiple sclerosis models, highlighting the diversity of microglial effects on the progression of demyelinating diseases and the strengths and weaknesses of microglial modulation in therapy design. 

Key words: astrocytes, colony-stimulating factor-1 receptor inhibition, cuprizone, demyelination, microglia, multiple sclerosis, neurodegeneration