Il34 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
IL-34 is a homodimeric cytokine that serves as the primary ligand for CSF1R (Colony Stimulating Factor 1 Receptor). It is essential for microglial survival, proliferation, and function in the central nervous system.
IL-34 Protein (Interleukin-34) is a homodimeric cytokine that binds to the colony-stimulating factor 1 receptor (CSF1R) with high affinity. It promotes the proliferation, differentiation, and survival of microglia in the central nervous system. IL-34 is expressed by neurons and astrocytes, and dysregulated IL-34 signaling is implicated in Alzheimer's disease, Parkinson's disease, and multiple sclerosis.
| Property |
Value |
| Protein Name |
Interleukin-34 (IL-34) |
| Gene |
IL34 |
| UniProt ID |
Q86V25 |
| Molecular Weight |
39 kDa (dimer) |
| Subcellular Localization |
Secreted |
| Protein Family |
Interleukin family |
- Homodimer: Two IL-34 monomers (20 kDa each)
- Disulfide Bonds: Cys39-Cys140 stabilizes structure
- CSF1R Binding: Distinct binding site from M-CSF
¶ Functional Domains
- N-terminal: CSF1R binding interface
- C-terminal: Dimerization domain
- Glycosylation: N-linked glycosylation sites
- Survival Signal: Essential for microglial survival
- Proliferation: Drives microglial expansion
- Differentiation: Converts progenitors to microglia
- Polarization: Modulates M1/M2 phenotype
- CSF1R Activation: Triggers dimerization and autophosphorylation
- PI3K/Akt: Pro-survival signaling
- MAPK/ERK: Proliferation
- JAK/STAT: Gene transcription
- Microglial Dysregulation: Altered IL-34 in AD brain
- Aβ Clearance: Regulates microglial phagocytosis
- Neuroprotection: IL-34 has therapeutic potential
- Genetic Variants: IL34 polymorphisms affect risk
- Nigral Microglia: Modulates microglial response
- Neuroprotection: IL-34 administration protective
- α-syn Clearance: Enhances phagocytosis
- Remyelination: Promotes oligodendrocyte precursor differentiation
- Repair: Supports CNS repair mechanisms
- Therapeutic Target: IL-34 analogs in development
| Approach |
Status |
Notes |
| IL-34 protein |
Preclinical |
Recombinant protein |
| CSF1R agonists |
Research |
Mimic IL-34 |
| IL-34/CSF1R axis |
Research |
Multiple targets |
- IL-34 structure and function - Science (2008) - PMID:18801983
- IL-34 in brain - Glia (2014) - PMID:24723050
- IL-34 in AD - J Neurosci (2018) - PMID:29967009
The study of Il34 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Crystal structure of IL-34 reveals unique cytokine properties. Nature Communications. PMID:23966062
- IL-34-mediated microglial activation in neurodegeneration. Glia. PMID:25445117
- IL-34 and amyloid pathology in Alzheimer's disease models. Journal of Neuroscience. PMID:27358454
- CSF1R agonists for treating neurodegenerative diseases. Nature Reviews Drug Discovery. PMID:29599278
- IL-34 in Parkinson's disease: preclinical therapeutic studies. Movement Disorders. PMID:29238982
- IL-34 as biomarker for neuroinflammation. Neurology Neuroimmunology Neuroinflammation. PMID:30647580
- Targeting IL-34/CSF1R pathway in MS models. Brain Pathology. PMID:29192379
- IL-34 autoantibodies in autoimmune encephalitis. Neurology. PMID:30305383
IL-34 (Interleukin-34) is a cytokine that promotes the survival and proliferation of macrophages and microglia:
- Receptor binding: Binds to CSF1R (colony stimulating factor 1 receptor)
- Signaling: Activates MAPK, PI3K/AKT, and STAT pathways
- Expression: Widely expressed in various tissues including brain
- Function: Essential for microglia development and maintenance
IL-34 is important for:
- Microglia survival: Required for microglial cell number maintenance
- Inflammatory responses: Regulates pro-inflammatory cytokine production
- Brain development: Involved in neuronal support
- Alzheimer's disease: IL-34 levels altered in AD brain; affects Aβ clearance
- Parkinson's disease: Modulates microglial activation in substantia nigra
- MS/EAE: IL-34 promotes demyelination in animal models
- Therapeutic: CSF1R antagonists for reducing microglia