Microglia as a critical player in both developmental and late-life CNS pathologies

Noël C. Derecki, Natalie Katzmarski, Jonathan Kipnis, Melanie Meyer-Luehmann

Research output: Contribution to journalReview articlepeer-review

45 Scopus citations

Abstract

Microglia, the tissue-resident macrophages of the brain, are attracting increasing attention as key players in brain homeostasis from development through aging. Recent works have highlighted new and unexpected roles for these once-enigmatic cells in both healthy central nervous system function and in diverse pathologies long thought to be primarily the result of neuronal malfunction. In this review, we have chosen to focus on Rett syndrome, which features early neurodevelopmental pathology, and Alzheimer's disease, a disorder associated predominantly with aging. Interestingly, receptor-mediated microglial phagocytosis has emerged as a key function in both developmental and late-life brain pathologies. In a mouse model of Rett syndrome, bone marrow transplant and CNS engraftment of microglia-like cells were associated with surprising improvements in pathology-these benefits were abrogated by block of phagocytic function. In Alzheimer's disease, large-scale genome-wide association studies have been brought to bear as a method of identifying previously unknown susceptibility genes, which highlight microglial receptors as promising novel targets for therapeutic modulation. Multi-photon in vivo microscopy has provided a method of directly visualizing the effects of manipulation of these target genes. Here, we review the latest findings and concepts emerging from the rapidly growing body of literature exemplified for Rett syndrome and late-onset, sporadic Alzheimer's disease.

Original languageEnglish
Pages (from-to)333-345
Number of pages13
JournalActa Neuropathologica
Volume128
Issue number3
DOIs
StatePublished - Sep 2014

Keywords

  • Alzheimer's disease
  • Amyloid plaques
  • Genome-wide association studies (GWAS)
  • In vivo two-photon microscopy
  • Mecp2
  • Microglia
  • Phagocytosis
  • Rett syndrome

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