Emerging Roles for CSF-1 Receptor and its Ligands in the Nervous System

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Abstract

The colony-stimulating factor-1 receptor (CSF-1R) kinase regulates tissue macrophage homeostasis, osteoclastogenesis, and Paneth cell development. However, recent studies in mice have revealed that CSF-1R signaling directly controls the development and maintenance of microglia, and cell autonomously regulates neuronal differentiation and survival. While the CSF-1R-cognate ligands, CSF-1 and interleukin-34 (IL-34) compete for binding to the CSF-1R, they are expressed in a largely non-overlapping manner by mature neurons. The recent identification of a dominantly inherited, adult-onset, progressive dementia associated with inactivating mutations in the CSF-1R highlights the importance of CSF-1R signaling in the brain. We review the roles of the CSF-1R and its ligands in microglial and neural development and function, and their relevance to our understanding of neurodegenerative disease. CSF-1R is a receptor tyrosine kinase with two cognate ligands, CSF-1 and IL-34, that are expressed in largely non-overlapping areas of the CNS and that regulate microglial proliferation, and survival.The CSF-1R is also expressed in neural progenitor cells and regulates their survival, proliferation and neuronal differentiation.Upregulation of CSF-1R expression in injured neurons promotes survival.Mutations in the CSF1R gene lead to an autosomal dominant, neurodegenerative disorder known as adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).The Csf1r +/- mouse is a validated model for testing therapeutic strategies for ALSP.CSF-1R ligands and inhibitors are potential modulators of several neurological diseases including Alzheimer's disease, globoid cell leukodystrophy (Krabbe's disease), Charcot-Marie-Tooth disease, multiple sclerosis, and glioma.

Original languageEnglish (US)
JournalTrends in Neurosciences
DOIs
StateAccepted/In press - 2016

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Macrophage Colony-Stimulating Factor Receptors
Colony-Stimulating Factor Receptors
Macrophage Colony-Stimulating Factor
Nervous System
Ligands
Globoid Cell Leukodystrophy
Interleukins
Neuroglia
Neurodegenerative Diseases
Paneth Cells
Charcot-Marie-Tooth Disease
Leukoencephalopathies
Neurons
Mutation
Receptor Protein-Tyrosine Kinases
Microglia
Osteogenesis

Keywords

  • Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia
  • IL-34
  • Microglia
  • Neural development
  • Neurodegenerative disease
  • Neuronal survival

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Emerging Roles for CSF-1 Receptor and its Ligands in the Nervous System",
abstract = "The colony-stimulating factor-1 receptor (CSF-1R) kinase regulates tissue macrophage homeostasis, osteoclastogenesis, and Paneth cell development. However, recent studies in mice have revealed that CSF-1R signaling directly controls the development and maintenance of microglia, and cell autonomously regulates neuronal differentiation and survival. While the CSF-1R-cognate ligands, CSF-1 and interleukin-34 (IL-34) compete for binding to the CSF-1R, they are expressed in a largely non-overlapping manner by mature neurons. The recent identification of a dominantly inherited, adult-onset, progressive dementia associated with inactivating mutations in the CSF-1R highlights the importance of CSF-1R signaling in the brain. We review the roles of the CSF-1R and its ligands in microglial and neural development and function, and their relevance to our understanding of neurodegenerative disease. CSF-1R is a receptor tyrosine kinase with two cognate ligands, CSF-1 and IL-34, that are expressed in largely non-overlapping areas of the CNS and that regulate microglial proliferation, and survival.The CSF-1R is also expressed in neural progenitor cells and regulates their survival, proliferation and neuronal differentiation.Upregulation of CSF-1R expression in injured neurons promotes survival.Mutations in the CSF1R gene lead to an autosomal dominant, neurodegenerative disorder known as adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).The Csf1r +/- mouse is a validated model for testing therapeutic strategies for ALSP.CSF-1R ligands and inhibitors are potential modulators of several neurological diseases including Alzheimer's disease, globoid cell leukodystrophy (Krabbe's disease), Charcot-Marie-Tooth disease, multiple sclerosis, and glioma.",
keywords = "Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia, IL-34, Microglia, Neural development, Neurodegenerative disease, Neuronal survival",
author = "Violeta Chitu and Solen Gokhan and Sayan Nandi and Mehler, {Mark F.} and Stanley, {E. Richard}",
year = "2016",
doi = "10.1016/j.tins.2016.03.005",
language = "English (US)",
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T1 - Emerging Roles for CSF-1 Receptor and its Ligands in the Nervous System

AU - Chitu, Violeta

AU - Gokhan, Solen

AU - Nandi, Sayan

AU - Mehler, Mark F.

AU - Stanley, E. Richard

PY - 2016

Y1 - 2016

N2 - The colony-stimulating factor-1 receptor (CSF-1R) kinase regulates tissue macrophage homeostasis, osteoclastogenesis, and Paneth cell development. However, recent studies in mice have revealed that CSF-1R signaling directly controls the development and maintenance of microglia, and cell autonomously regulates neuronal differentiation and survival. While the CSF-1R-cognate ligands, CSF-1 and interleukin-34 (IL-34) compete for binding to the CSF-1R, they are expressed in a largely non-overlapping manner by mature neurons. The recent identification of a dominantly inherited, adult-onset, progressive dementia associated with inactivating mutations in the CSF-1R highlights the importance of CSF-1R signaling in the brain. We review the roles of the CSF-1R and its ligands in microglial and neural development and function, and their relevance to our understanding of neurodegenerative disease. CSF-1R is a receptor tyrosine kinase with two cognate ligands, CSF-1 and IL-34, that are expressed in largely non-overlapping areas of the CNS and that regulate microglial proliferation, and survival.The CSF-1R is also expressed in neural progenitor cells and regulates their survival, proliferation and neuronal differentiation.Upregulation of CSF-1R expression in injured neurons promotes survival.Mutations in the CSF1R gene lead to an autosomal dominant, neurodegenerative disorder known as adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).The Csf1r +/- mouse is a validated model for testing therapeutic strategies for ALSP.CSF-1R ligands and inhibitors are potential modulators of several neurological diseases including Alzheimer's disease, globoid cell leukodystrophy (Krabbe's disease), Charcot-Marie-Tooth disease, multiple sclerosis, and glioma.

AB - The colony-stimulating factor-1 receptor (CSF-1R) kinase regulates tissue macrophage homeostasis, osteoclastogenesis, and Paneth cell development. However, recent studies in mice have revealed that CSF-1R signaling directly controls the development and maintenance of microglia, and cell autonomously regulates neuronal differentiation and survival. While the CSF-1R-cognate ligands, CSF-1 and interleukin-34 (IL-34) compete for binding to the CSF-1R, they are expressed in a largely non-overlapping manner by mature neurons. The recent identification of a dominantly inherited, adult-onset, progressive dementia associated with inactivating mutations in the CSF-1R highlights the importance of CSF-1R signaling in the brain. We review the roles of the CSF-1R and its ligands in microglial and neural development and function, and their relevance to our understanding of neurodegenerative disease. CSF-1R is a receptor tyrosine kinase with two cognate ligands, CSF-1 and IL-34, that are expressed in largely non-overlapping areas of the CNS and that regulate microglial proliferation, and survival.The CSF-1R is also expressed in neural progenitor cells and regulates their survival, proliferation and neuronal differentiation.Upregulation of CSF-1R expression in injured neurons promotes survival.Mutations in the CSF1R gene lead to an autosomal dominant, neurodegenerative disorder known as adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).The Csf1r +/- mouse is a validated model for testing therapeutic strategies for ALSP.CSF-1R ligands and inhibitors are potential modulators of several neurological diseases including Alzheimer's disease, globoid cell leukodystrophy (Krabbe's disease), Charcot-Marie-Tooth disease, multiple sclerosis, and glioma.

KW - Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia

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KW - Neurodegenerative disease

KW - Neuronal survival

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