Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival

Luo, Jian; Elwood, Fiona; Britschgi, Markus; Villeda, Saul; Zhang, Hui; Ding, Zhaoqing; Zhu, Liyin; Alabsi, Haitham; Getachew, Ruth; Narasimhan, Ramya; Wabl, Rafael; Fainberg, Nina; James, Michelle L.; Wong, Gordon Tin Chun; Relton, Jane K.; Gambhir, Sanjiv S.; Pollard, Jeffrey W.; Wyss‐Coray, Tony

doi:10.1084/jem.20120412

Cited by 212 publications

(218 citation statements)

References 78 publications

(174 reference statements)

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“…Increased expression of LRP1 was observed in PD brain (38) and functional soluble LRP1 was also detected in human brain tissue and CSF (39). Colony-stimulating factor receptor 1 (CSFR1) is the receptor for colony stimulating factor 1 and interleukin-34 (IL-34), which are key regulators of the monocyte/macrophage lineage (40). In a mouse model lacking CSFR1, neurons are more susceptible to cell death and neu- rodegeneration after excitotoxic injury, suggesting involvement of CSFR1 signaling in their survival (40).…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Peptides as Potential Parkinson Disease Biomarkers: A Staged Pipeline for Discovery and Validation*

Shi

Movius

Dator

et al. 2015

Molecular & Cellular Proteomics

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a Finding robust biomarkers for Parkinson disease (PD) is currently hampered by inherent technical limitations associated with imaging or antibody-based protein assays.To circumvent the challenges, we adapted a staged pipeline, starting from our previous proteomic profiling followed by high-throughput targeted mass spectrometry (MS), to identify peptides in human cerebrospinal fluid (CSF) for PD diagnosis and disease severity correlation. In this multicenter study consisting of training and validation sets, a total of 178 subjects were randomly selected from a retrospective cohort, matching age and sex between PD patients, healthy controls, and neurological controls with Alzheimer disease (AD). From ϳ14,000 unique peptides displaying differences between PD and healthy control in proteomic investigations, 126 peptides were selected based on relevance and observability in CSF using bioinformatic analysis and MS screening, and then quantified by highly accurate and sensitive selected reaction monitoring (SRM) in the CSF of 30 PD patients versus 30 healthy controls (training set), followed by diagnostic (receiver operating characteristics) and disease severity correlation analyses. The most promising candidates were further tested in an independent cohort of 40 PD patients, 38 AD patients, and 40 healthy controls (validation set). A panel of five peptides (derived from SPP1, LRP1, CSF1R, EPHA4, and TIMP1) was identified to provide an area under curve (AUC) of 0.873 (sensitivity ‫؍‬ 76.7%, specificity ‫؍‬ 80.0%) for PD versus healthy controls in the training set. The performance was essentially confirmed in the validation set (AUC ‫؍‬ 0.853, sensitivity ‫؍‬ 82.5%, specificity ‫؍‬ 82.5%). Additionally, this panel could also differentiate the PD and AD groups (AUC ‫؍‬ 0.990, sensitivity ‫؍‬ 95.0%, specificity ‫؍‬ 97.4%). Furthermore, a combination of two peptides belonging to proteins TIMP1 and APLP1 significantly correlated with disease severity as determined by the Unified Parkinson's Disease Rating Scale motor scores in both the training (r ‫؍‬ 0.381, p ‫؍‬ 0.038)j and the validation (r ‫؍‬ 0.339, p ‫؍‬ 0.032) sets. The novel panel of CSF peptides, if validated in independent co-

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Peptides as Potential Parkinson Disease Biomarkers: A Staged Pipeline for Discovery and Validation*

Shi

Movius

Dator

et al. 2015

Molecular & Cellular Proteomics

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“…Although targeting CSF1R has therapeutic potential, caution should be taken, as CSF1R haploinsufficiency was linked to adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (145). Additionally, CSF1R signaling in a selected neuron population, rather than in microglia, provides neuroprotective and survival signals in the neurodegeneration setting (146).…”

Section: R E V I E W S E R I E S : G L I a A N D N E U R O D E G E Nmentioning

confidence: 99%

Microglia in Alzheimer’s disease

Sarlus

Heneka

2017

Journal of Clinical Investigation

698

561

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“…It is also expressed on oocytes and preimplantation embryos, decidual and trophoblastic cells (reviewed in Pollard and Stanley 1996), neural progenitor cells and other neuronal cells (Wang et al 1999a;Nandi et al 2012;Luo et al 2013), renal proximal tubule epithelial cells, and colonic epithelial cells (reviewed in Chitu and Stanley 2014). The broad pattern of expression of CSF-1R is consistent with its pleiotropic actions in embryonic development, adult physiology, innate immunity, inflammation, tissue repair, and in the tumor microenvironment (reviewed in Chitu and Stanley 2014).…”

Section: Csf-1r Expressionmentioning

confidence: 99%

CSF-1 Receptor Signaling in Myeloid Cells

Stanley

Chiţu

2014

Cold Spring Harbor Perspectives in Biology

634

521

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The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). It plays important roles in development and in innate immunity by regulating the development of most tissue macrophages and osteoclasts, of Langerhans cells of the skin, of Paneth cells of the small intestine, and of brain microglia. It also regulates the differentiation of neural progenitor cells and controls functions of oocytes and trophoblastic cells in the female reproductive tract. Owing to this broad tissue expression pattern, it plays a central role in neoplastic, inflammatory, and neurological diseases. In this review we summarize the evolution, structure, and regulation of expression of the CSF-1R gene. We discuss the structures of CSF-1, IL-34, and the CSF-1R and the mechanism of ligand binding to and activation of the receptor. We further describe the pathways regulating macrophage survival, proliferation, differentiation, and chemotaxis downstream from the CSF-1R.

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Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival

Abstract: Colony-stimulating factor 1 and IL-34 protect against and partially reverse neurodegeneration in mice in part via promoting CREB signaling.

Cited by 212 publications

References 78 publications

Cerebrospinal Fluid Peptides as Potential Parkinson Disease Biomarkers: A Staged Pipeline for Discovery and Validation*

Cerebrospinal Fluid Peptides as Potential Parkinson Disease Biomarkers: A Staged Pipeline for Discovery and Validation*

Microglia in Alzheimer’s disease

CSF-1 Receptor Signaling in Myeloid Cells

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