Microglia and Macrophages

Microglia are the primary resident immune cells of the central nervous system, while macrophages are myeloid cells that reside in peripheral tissues or infiltrate the brain during pathological events (Prinz et al., 2019, Nature Reviews Immunology). These cells are responsible for immune surveillance, phagocytosis of debris, and the release of cytokines that modulate the inflammatory environment (Butovsky & Weiner, 2018, Nature Reviews Neuroscience). In diseases such as Alzheimer's, Parkinson's, and various cancers, microglia and macrophages can become chronically activated or adopt immunosuppressive roles that exacerbate tissue damage or promote tumor growth (Ulland & Colonna, 2018, Nature Reviews Immunology). While they are critical focal points for therapeutic development, "Microglia/Macrophages" refers to cell populations rather than a single molecular target like a receptor or enzyme. Consequently, drug discovery efforts typically focus on specific proteins expressed by these cells, such as the Colony-stimulating factor 1 receptor (CSF1R) or Triggering receptor expressed on myeloid cells 2 (TREM2), to modulate their function (Cannarile et al., 2017, Journal for ImmunoTherapy of Cancer). Targeting these cells requires a nuanced approach to balance the reduction of neuroinflammation with the preservation of their essential homeostatic and neuroprotective functions. Biomarkers like the Translocator protein (TSPO) are often used in clinical imaging to monitor the activation state of these cells in patients (Politis et al., 2012, Brain).

Other names

Microglial cellsMonocyte-derived macrophagesCNS resident macrophagesMyeloid cells

Modulation of cellular activation states, inhibition of pro-inflammatory cytokine release, or depletion of specific cell populations via inhibition of survival signaling pathways such as the Colony-stimulating factor 1 receptor (CSF1R) (Cannarile et al., 2017, Journal for ImmunoTherapy of Cancer).