Inhibition of colony stimulating factor-1 receptor (CSF-1R) as a potential therapeutic strategy for neurodegenerative diseases: opportunities and challenges

Cell Mol Life Sci. 2022 Apr 2;79(4):219. doi: 10.1007/s00018-022-04225-1.

Abstract

Microglia are specialized dynamic immune cells in the central nervous system (CNS) that plays a crucial role in brain homeostasis and in disease states. Persistent neuroinflammation is considered a hallmark of many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and primary progressive multiple sclerosis (MS). Colony stimulating factor 1-receptor (CSF-1R) is predominantly expressed on microglia and its expression is significantly increased in neurodegenerative diseases. Cumulative findings have indicated that CSF-1R inhibitors can have beneficial effects in preclinical neurodegenerative disease models. Research using CSF-1R inhibitors has now been extended into non-human primates and humans. This review article summarizes the most recent advances using CSF-1R inhibitors in different neurodegenerative conditions including AD, PD, HD, ALS and MS. Potential challenges for translating these findings into clinical practice are presented.

Keywords: Alzheimer’s disease; Amyotrophic lateral sclerosis; Colony stimulating factor-1 receptor; Huntington’s disease; Multiple sclerosis; Parkinson’s disease.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Animals
  • Colony-Stimulating Factors / pharmacology
  • Colony-Stimulating Factors / therapeutic use
  • Microglia / metabolism
  • Neurodegenerative Diseases* / drug therapy
  • Neurodegenerative Diseases* / metabolism
  • Parkinson Disease* / drug therapy

Substances

  • Colony-Stimulating Factors