Present and future of microglial pharmacology

Trends Pharmacol Sci. 2022 Aug;43(8):669-685. doi: 10.1016/j.tips.2021.11.006. Epub 2022 Jan 11.

Abstract

Microglia, brain resident immune cells, modulate development, activity, and plasticity of the central nervous system. Mechanistically implicated in numerous neurological pathologies, microglia emerge as strong contenders for novel neurotherapies. Shifting away from merely an attenuation of excessive microglial inflammatory and phagocytic activities, current therapies aim toward targeting the complex context-dependent microglial heterogeneity, unveiled by large-scale genetic studies and emerging single-cell analyses. Although lacking the necessary selectivity, initial therapies attempting to target specific state-associated microglial properties and functions (e.g., inflammatory activity, phagocytosis, proliferation, metabolism, or surveillance) are currently under pre- or even clinical (Phase I-IV) investigation. Here, we provide an update on current microglial therapeutic research and discuss what the future in the field might look like.

Keywords: microglia; microglial heterogeneity; neurological disease; selective targeting; therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Brain / metabolism
  • Drug Delivery Systems*
  • Humans
  • Microglia*
  • Phagocytosis / physiology

Grants and funding