Colony-stimulating factor 1 receptor signaling in the central nervous system and the potential of its pharmacological inhibitors to halt the progression of neurological disorders
Abstract
Colony Stimulating Factor-1 (CSF-1)/Colony Stimulating Factor-1 Receptor (CSF-1R) signaling axis plays an essential role in the development, maintenance, and proliferation of macrophage lineage cells. Within the central nervous system, CSF-1R signaling primarily maintains microglial homeostasis. Microglia, being the resident macrophage and first responder to any neurological insults, plays critical importance in overall health of the human brain. Aberrant and sustained activation of microglia along with continued proliferation and release of neurotoxic proinflammatory cytokines have been reported in various neurological and neurodegenerative diseases. Therefore, halting the neuroinflammatory pathway via targeting microglial proliferation, which depends on CSF-1R signaling, has emerged as a potential therapeutic target for neurological disorders. However, apart from regulating the microglial function, recently it has been discovered that CSF-1R has much broader role in central nervous system. These findings limit the therapeutic utility of CSF-1R inhibitors but also highlight the need for a complete understanding of CSF-1R function within the central nervous system. Moreover, it has been found that selective inhibitors of CSF-1R may be more efficient in avoiding non-specific targeting and associated side effects. Short-term depletion of microglial population in diseased conditions have also been found to be beneficial; however, the dose and therapeutic window for optimum effec…
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Differing outcomes have been reported with microglial depletion.
“and differing outcomes have also been reported with microglial depletion.45,46”
From Microglial <i>INPP5D</i> limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [46]
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“45,46 Notably, the timing of gene and/or total microglial manipulation is also critical, 47 and as we noted, we deliberately used conditional knockdown early in “disease” stage to mimic what might be therapeutically viable.”
- Authors
- Tarale, P., & Alam, M. M.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Tarale, Prashant
- Venue
- Inflammopharmacology
- Published
- 2022-03-15
- Volume
- 30
- Issue
- 3
- Pages
- 821-842
- ISSN
- 0925-4692 (ISSN-L)
- 1568-5608
- OpenAlex
- W4221089587
- Cited by
- 26
- References
- 27
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 7 · 2023: 1 · 2022: 3
- FWCI
- 0.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Inflammopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- CSF-1 receptor, microglia, neuroinflammation, neurodegenerative diseases, CSF1R inhibitor, microglial depletion, neuronal function, macrophage lineage, inflammatory cytokines, central nervous system
- MeSH terms
- Central Nervous System, Humans, Signal Transduction, Macrophage Colony-Stimulating Factor, Receptor, Macrophage Colony-Stimulating Factor, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Microglia, Neurodegenerative Diseases
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