CCL2 and Neuronal Inflammation: Implications for Neurodegenerative Diseases

Abstract

Microglia, the resident immune cells of the central nervous system, play a pivotal role in maintaining brain homeostasis and responding to various pathological conditions1,2. 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 responses3-5. Additionally, we examine the implications of CCL2-mediated neuroinflammation in neurodegenerative disorders such as Alzheimers disease6,7, Parkinsons disease8, and amyotrophic lateral sclerosis. Lastly, we discuss potential therapeutic strategies targeting the microglial CCL2 axis to modulate neuroinflammation and ameliorate neurodegenerative processes.