The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer's disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.
Ligand and protein kinase C downmodulate the colony-stimulating factor 1 receptor by independent mechanisms.
Interleukin 2 down-modulates the macrophage colony-stimulating factor receptor in murine macrophages
Interleukin-4 rapidly down-modulates the macrophage colony-stimulating factor receptor in murine macrophages
TNF-alpha-converting enzyme cleaves the macrophage colony-stimulating factor receptor in macrophages undergoing activation
Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects.
Phorbol 12-myristate 13-acetate-induced release of the colony-stimulating factor 1 receptor cytoplasmic domain into the cytosol involves two separate cleavage events.
A novel soluble form of the CSF-1 receptor inhibits proliferation of self-renewing macrophages of goldfish (Carassius auratus L.)
Presenilin/gamma-secretase-dependent processing of beta-amyloid precursor protein regulates EGF receptor expression
CSF-1 and TPA stimulate independent pathways leading to lysosomal degradation or regulated intramembrane proteolysis of the CSF-1 receptor.
Toll-like receptors stimulate regulated intramembrane proteolysis of the CSF-1 receptor through Erk activation.
Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation.
A novel function of colony-stimulating factor 1 receptor in hTERT immortalization of human epithelial cells
Selective reduction in microglia density and function in the white matter of colony-stimulating factor-1-deficient mice.
Macrophage colony-stimulating factor induces the proliferation and survival of macrophages via a pathway involving DAP12 and beta-catenin.
Systematic identification of cell cycle-dependent yeast nucleocytoplasmic shuttling proteins by prediction of composite motifs.
Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits.
Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids
National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease.
The CSF-1 receptor ligands IL-34 and CSF-1 exhibit distinct developmental brain expression patterns and regulate neural progenitor cell maintenance and maturation.
IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia.
Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia.
Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival
A case of hereditary diffuse leukoencephalopathy with axonal spheroids caused by a de novo mutation in CSF1R masquerading as primary progressive multiple sclerosis
Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations
A new CSF1R mutation presenting with an extensive white matter lesion mimicking primary progressive multiple sclerosis
Sequential proteolytic processing of the triggering receptor expressed on myeloid cells-2 (TREM2) protein by ectodomain shedding and γ-secretase-dependent intramembranous cleavage.
Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain
Alzheimer's Disease: Microglia
Microglia are a type of glial cell found throughout the brain and spinal cord. Microglia have been found to be associated with Alzheimer's disease development and progression. Here are the latest discoveries pertaining to Alzheimer's disease and microglia.