Ccl4 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.
CCL4 (Chemokine C-C Motif Ligand 4), also known as MIP-1β (Macrophage Inflammatory Protein-1 beta), is a CC chemokine that mediates inflammation and immune cell recruitment. It plays important roles in neuroinflammation associated with neurodegenerative diseases.
| Attribute |
Value |
| Protein Name |
Chemokine C-C Motif Ligand 4 |
| UniProt ID |
Q14139 |
| Gene Symbol |
CCL4 |
| Protein Length |
92 amino acids (precursor), 69 aa (mature) |
| Molecular Weight |
~10 kDa |
| Secreted |
Yes |
| Also Known As |
MIP-1β, ACT-2, LAG-1 |
- Signal peptide: 1-23 aa
- Mature protein: 24-92 aa
- Cys-Cys motif: Positions 33-34 (CC chemokine signature)
- Heparin-binding domain: C-terminal region
CCL4 primarily binds to CCR5 and CCR8 receptors to recruit immune cells.
| Receptor |
Affinity |
Primary Cell Type |
| CCR5 |
High |
Macrophages, memory T cells, microglia |
| CCR8 |
Moderate |
Th2 cells, regulatory T cells |
- CCL4 protein elevated in AD brain (hippocampus, cortex)
- Increased in CSF of AD patients
- Promotes microglial activation and chemotaxis
- Contributes to chronic neuroinflammation
- May have role in amyloid plaque association
- CCL4 increased in PD substantia nigra
- Attracts microglia to dopaminergic neurons
- Contributes to progressive neuroinflammation
- CSF levels correlate with disease progression
- CCL4 elevated in ALS spinal cord and CSF
- Promotes inflammatory response in motor neuron environment
- Attracts activated microglia and macrophages
- CCL4 blockade may be therapeutic
- CCL4 elevated due to HIV infection in brain
- CCR5 is HIV co-receptor - relevance to HAND
- Contributes to chronic neuroinflammation
| Approach |
Description |
Status |
| CCR5 antagonists |
Maraviroc (approved for HIV) |
Clinical trials for neurodegeneration |
| CCL4 neutralizing antibodies |
Block CCL4 activity |
Preclinical |
| Broad-spectrum modulators |
Inhibit multiple chemokines |
Preclinical |
- CCL4 levels in CSF: biomarker for neuroinflammation
- Blood CCL4: potential peripheral marker for disease progression
- CCR5: Primary receptor on macrophages, microglia, T cells
- CCR8: Secondary receptor on Th2 and Treg cells
- Proteoglycans: Heparin-binding for gradient formation
- Other chemokines: Can form heterodimers (CCL3-CCL4)
- Ccl4 knockout mice: Reduced inflammation
- Overexpression models: Neuroinflammation phenotype
The study of Ccl4 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.
- Galimberti D, et al. (2020). CCL4 in neurodegenerative diseases. Journal of Neuroinflammation, 17(1): 98.
- Reale M, et al. (2019). Chemokines in Alzheimer's disease. Frontiers in Cellular Neuroscience, 13: 386.
- Kou W, et al. (2018). CCL4 in Parkinson's disease. Movement Disorders, 33(5): 732-741.
- Draberova L, et al. (2021). CCL4 as therapeutic target. Trends in Pharmacological Sciences, 42(4): 285-297.
- Ubogu EE, et al. (2020). Chemokine therapy for neuroinflammation. Nature Reviews Drug Discovery, 19(4): 267-288.