CCL2 and Neuronal Inflammation: Implications for Neurodegenerative Diseases
Open accessAbstract
Microglia, the resident immune cells of the central nervous system, play a pivotal role in maintaining brain homeostasis and responding to various pathological conditions 1,2 . Neuroinflammation, characterized by the activation of microglia and subsequent release of pro-inflammatory cytokines, has been implicated in the pathogenesis of numerous neurodegenerative diseases. Among these cytokines, chemokine (C-C motif) ligand 2 (CCL2) has gained significant attention due to its role in attracting immune cells and its potential contribution to neuronal inflammation. This review aims to comprehensively elucidate the involvement of microglial CCL2 in neuronal inflammation and its relevance to neurodegenerative diseases. We discuss the molecular mechanisms underlying CCL2 production, its receptors on neurons, and the downstream signaling pathways that initiate and perpetuate neuroinflammation. Furthermore, we explore the bidirectional communication between microglia and neurons, highlighting how neuronal dysfunction can trigger microglial CCL2 release and subsequent immune responses 3-5 . Additionally, we examine the implications of CCL2-mediated neuroinflammation in neurodegenerative disorders such as Alzheimer’s disease 6,7 , Parkinson’s disease 8 , and amyotrophic lateral sclerosis. Lastly, we discuss potential therapeutic strategies targeting the microglial CCL2 axis to modulate neuroinflammation and ameliorate neurodegenerative processes.
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CCL2 has the known capacity to break down the blood brain barrier and recruit peripheral immune cells to sites of damage.
“consistent with the known capacity of CCL2 to break down the blood brain barrier and recruit peripheral immune cells to sites of damage.58–62”
From TET2-mutant myeloid cells mitigate Alzheimer’s disease progression via CNS infiltration and enhanced phagocytosis in mice (2025) · cites this paper as [61]
The Introduction (page unavailable) describes CCL2 as a potent chemoattractant for monocytes and immune cells, supporting the recruitment aspect in general. It does not specify recruitment of peripheral cells to damage sites, and the passages found do not say that CCL2 breaks down the blood–brain barrier. (LLM, conf=0.86)
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Cites
Microglia Heterogeneity in the Single-Cell Era
Masuda, T., Sankowski, R., Staszewski, O., & Prinz, M. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.010 · Cited by 784 · see citing works
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Matatall, K. A., Wathan, T. K., Nguyen, M., Chen, H., McDonald, A., Qi, G., Belk, J. A., Florez, M. A., Le, D. T., Olarinde, T., et al. (2025) · Cell Stem Cell · doi:10.1016/j.stem.2025.06.006 · Cited by 23 · see citing works
- Authors
- zihang, Z., qingyi, M., tianhuan, Q., & Si-Yan, L.
- Affiliations
- Zunyi Medical University (CN)
- Lanzhou University (CN)
- Corresponding author
- Si-Yan, Li
- ORCID
- zihang, Zeng
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2023-08-17
- OpenAlex
- W4386007960
- Cited by
- 5
- References
- 1
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1
- Type
- posted content
- Language
- en
- Open access
- green
- dx.doi.org
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- MCP-1, neuroinflammation, microglia, neurodegenerative diseases, chemokines, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, inflammatory cytokines
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