CCL4 is a human gene. Variants in CCL4 have been implicated in Alzheimer's Disease, Parkinson's Disease, Multiple Sclerosis. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration. [1]
CCL4 (C-C motif chemokine ligand 4), also known as MIP-1β (macrophage inflammatory protein 1 beta), is a member of the CC chemokine family that plays critical roles in immune cell recruitment and neuroinflammation. The CCL4 protein is a key mediator of microglial activation and neuroinflammatory responses that contribute to the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS) 1. Understanding CCL4's role in neuroinflammation provides insights into therapeutic targeting of immune pathways in neurodegeneration. [2]
| Feature | Details | [3]
|---------|---------| [4]
| Gene Symbol | CCL4 | [5]
| Full Name | C-C motif chemokine ligand 4 | [6]
| Synonyms | MIP-1β, ACT-2, HC21, LAG-1, G-26, MIPA, MIP1B, SCYA4 | [7]
| Chromosomal Location | 17q12 | [8]
| NCBI Gene ID | 6351 | [9]
| Ensembl ID | ENSG00000129277 | [10]
| Protein Size | 92 amino acids (precursor), 69 amino acids (mature) | [11]
| Molecular Weight | ~10 kDa (mature peptide) | [12]
The CCL4 gene is located on chromosome 17q12 and encodes a secreted chemokine that functions as a chemoattractant for various immune cells 2. The gene consists of 3 exons and encodes a precursor protein that is processed to generate the mature, biologically active form. [13]
CCL4 exerts its biological effects by binding to specific chemokine receptors, primarily CCR5 and CCR8 3: [14]
Upon receptor binding, CCL4 triggers: [15]
The CCL4-CCR5 interaction activates multiple downstream pathways 4: [16]
CCL4 is a potent activator of microglial cells, the resident immune cells of the central nervous system 6: [17]
Microglial activation is a hallmark of neurodegenerative diseases, and CCL4 serves as a critical chemokine linking peripheral immune responses to CNS inflammation 7. [18]
CCL4 participates in the neuroinflammatory cascade that characterizes neurodegenerative diseases: [19]
CCL4 is elevated in AD brains and cerebrospinal fluid (CSF), correlating with disease severity 7:
Mechanisms in AD:
CCL4 contributes to neuroinflammation in PD through multiple mechanisms 8:
CCL4 plays a complex role in MS pathogenesis 15:
CCL4 is elevated in ALS and contributes to motor neuron degeneration 19:
CCL4 is elevated in HD and contributes to the neuroinflammatory phenotype 21:
CCL4 has been investigated as a biomarker for neurodegenerative diseases:
The CCL4-CCR5 axis is a promising therapeutic target:
CCR5 Antagonists:
CCL4 Neutralizing Antibodies:
Zuro JM, et al. CSF chemokine levels in AD (2015). 2015. ↩︎
Hall S, et al. CCL4 in preclinical Alzheimer's (2017). 2017. ↩︎
Chatterjee S, et al. CCL4 in PD post-mortem brains (2019). 2019. ↩︎
Sanchez M, et al. CCL4 as PD biomarker (2021). 2021. ↩︎
Simpson LJ, et al. CCL4 in multiple sclerosis (2010). 2010. ↩︎
Matsuda A, et al. CCR5 antagonists in MS (2015). 2015. ↩︎
Bhasin JM, et al. CCL4 and demyelination (2011). 2011. ↩︎
Lui AJ, et al. CCL4 in ALS (2019). 2019. ↩︎
Zhang L, et al. CCR5 blockade in ALS models (2020). 2020. ↩︎
Wild E, et al. CCL4 in Huntington's disease (2011). 2011. ↩︎
Kumar A, et al. Neuroinflammation in HD (2020). 2020. ↩︎
Wang X, et al. CCL4 in stroke (2013). 2013. ↩︎
Jin G, et al. CCL4 inhibition reduces infarct size (2015). 2015. ↩︎
Zhang K, et al. CCL4 transgenic mice (2014). 2014. ↩︎
Matsumoto T, et al. MIP-1 beta knockout mice (1997). 1997. ↩︎
Chen Y, et al. AAV-CCL4 in brain (2018). 2018. ↩︎
Yang D, et al. CCL4 effects on microglia (2017). 2017. ↩︎
Nakai Y, et al. CCL4 in organotypic slices (2014). 2014. ↩︎
Speidel A, et al. CCL4 on iPSC neurons (2020). 2020. ↩︎