Microglia: Multiple roles in surveillance, circuit shaping, and response to injury

Dr. Benarroch[1] provided an excellent overview of the role of microglia. Microglia are implicated in many neurodegenerative disorders and we noted that the newly identified colony stimulating factor 1 receptor (CSF1R) gene mutation is causative for hereditary diffuse leukoencephalopathy with spheroids (HDLS).[2] HDLS is an inherited progressive disorder of axons and myelin with a variable phenotype, mimicking other disorders such as primary progressive multiple sclerosis, frontotemporal dementia, other dementias and atypical parkinsonian disorders.[2,3] The CSF1R gene encodes a tyrosine kinase transmembrane receptor for the cytokine CSF1, which is trophic for phagocytic cells of the myeloid lineage including microglia, and for interleukin 34 (IL-34).[4] It has been established that lipid-laden microglia are a consistent microscopic finding in HDLS pathology. The CSF1R gene mutation thus establishes HDLS as a microgliopathy.[2] However, the exact mechanism is unclear. It may be related to an abnormal innate immune response predisposing to neurodegeneration. Discovering the role of CSF1R signaling in HDLS might offer novel insights into microglial physiology and the involvement of this cell type in neurodegeneration.