Pharmacological inhibition of CSF1R by GW2580 reduces microglial proliferation and is protective against neuroinflammation and dopaminergic neurodegeneration.
Title
Pharmacological inhibition of CSF1R by GW2580 reduces microglial proliferation and is protective against neuroinflammation and dopaminergic neurodegeneration.
Creator
Neal Matthew L; Fleming Sheila M; Budge Kevin M; Boyle Alexa M; Kim Chunki; Alam Gelareh; Beier Eric E; Wu Long‐Jun; Richardson Jason R
Publisher
FASEB Journal
Date
2020
2020-01
Description
Increased pro‐inflammatory cytokine levels and proliferation of activated microglia have been found in Parkinson's disease (PD) patients and animal models of PD, suggesting that targeting of the microglial inflammatory response may result in neuroprotection in PD. Microglial proliferation is regulated by many factors, but colony stimulating factor‐1 receptor (CSF1R) has emerged as a primary factor. Using data mining techniques on existing microarray data, we found that mRNA expression of the CSF1R ligand, CSF‐1, is increased in the brain of PD patients compared to controls. In two different neurotoxic mouse models of PD, acute MPTP and sub‐chronic LPS treatment, mRNA and protein levels of CSF1R and CSF‐1 were significantly increased. Treatment with the CSF1R inhibitor GW2580 significantly attenuated MPTP‐induced CSF1R activation and Iba1‐positive cell proliferation, without a reduction of the basal Iba1‐positive population in the substantia nigra. GW2580 treatment also significantly decreased mRNA levels of pro‐inflammatory factors, without alteration of anti‐inflammatory mediators, and significantly attenuated the MPTP‐induced loss of dopamine neurons and motor behavioral deficits. Importantly, these effects were observed in the absence of overt microglial depletion, suggesting that targeting CSF1R signaling may be a viable neuroprotective strategy in PD that disrupts pro‐inflammatory signaling, but maintains the beneficial effects of microglia. [ABSTRACT FROM AUTHOR]
Subject
microglia; neuroprotection; Parkinson's disease; proliferation
Identifier
Format
Journal Article
URL Address
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Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Pages
1679-1694
Issue
1
Volume
34
ISSN
8926638
NEOMED College
NEOMED College of Pharmacy
NEOMED Department
Department of Pharmaceutical Sciences
Update Year & Number
January 2020 Update
Citation
Neal Matthew L; Fleming Sheila M; Budge Kevin M; Boyle Alexa M; Kim Chunki; Alam Gelareh; Beier Eric E; Wu Long‐Jun; Richardson Jason R, “Pharmacological inhibition of CSF1R by GW2580 reduces microglial proliferation and is protective against neuroinflammation and dopaminergic neurodegeneration.,” NEOMED Bibliography Database, accessed April 18, 2025, https://neomed.omeka.net/items/show/10923.