Microglia as therapeutic target in central nervous system disorders

J Pharmacol Sci. 2020 Nov;144(3):102-118. doi: 10.1016/j.jphs.2020.07.004. Epub 2020 Aug 15.

Abstract

Chronic microglial activation is associated with the pathogenesis of several CNS disorders. Microglia show phenotypic diversity and functional complexity in diseased CNS. Thus, understanding the pathology-specific heterogeneity of microglial behavior is crucial for the future development of microglia-modulating therapy for variety of CNS disorders. This review summarizes up-to-date knowledge on how microglia contribute to CNS homeostasis during development and throughout adulthood. We discuss the heterogeneity of microglial phenotypes in the context of CNS disorders with an emphasis on neurodegenerative diseases, demyelinating diseases, CNS trauma, and epilepsy. We conclude this review with a discussion about the disease-specific heterogeneity of microglial function and how it could be exploited for therapeutic intervention.

Keywords: CNS disorders; Heterogeneity; Homeostasis; Microglial activation; Phenotypes.

Publication types

  • Review

MeSH terms

  • Central Nervous System Diseases / etiology*
  • Central Nervous System Diseases / pathology
  • Central Nervous System Diseases / therapy*
  • Demyelinating Diseases / etiology
  • Demyelinating Diseases / pathology
  • Demyelinating Diseases / therapy
  • Epilepsy / etiology
  • Epilepsy / pathology
  • Epilepsy / therapy
  • Homeostasis
  • Humans
  • Microglia / pathology*
  • Microglia / physiology*
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / therapy
  • Phenotype