Fractalkine (CX3CL1) signaling and neuroinflammation in Parkinson’s disease: Potential clinical and therapeutic implications

• Published in: Pharmacological research Vol. 158; p. 104930
• Main Authors: Angelopoulou, Efthalia, Paudel, Yam Nath, Shaikh, Mohd. Farooq, Piperi, Christina
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.08.2020
• Subjects: CX3CL1; CX3CR1; Fractalkine; Neuroinflammation; Parkinson’s disease; CX3CR1; Neuroinflammation; Fractalkine; CX3CL1; Parkinson’s disease; neuroinflammation
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2020.104930

[Display omitted] Neuroinflammation plays a crucial role in the pathogenesis of Parkinson’s disease (PD) with the dysregulation of microglial activity being tightly linked to dopaminergic degeneration. Fractalkine (CX3CL1), a chemokine mainly expressed by neurons, can modulate microglial activity through binding to its sole G-protein-coupled receptor (CX3CR1), expressed by microglia. Fractalkine/CX3CR1 signaling is one of the most important mediators of the communication between neurons and microglia, and its emerging role in neurodegenerative disorders including PD has been increasingly recognized. Pre-clinical evidence has revealed that fractalkine signaling axis exerts dual effects on PD-related inflammation and degeneration, which greatly depend on the isoform type (soluble or membrane-bound), animal model (mice or rats, toxin- or proteinopathy-induced), route of toxin administration, time course and specific brain region (striatum, substantia nigra). Furthermore, although existing clinical evidence is scant, it has been indicated that fractalkine may be possibly associated with PD progression, paving the way for future studies investigating its biomarker potential. In this review, we discuss recent evidence on the role of fractalkine/CX3CR1 signaling axis in PD pathogenesis, aiming to shed more light on the molecular mechanisms underlying the neuroinflammation commonly associated with the disease, as well as potential clinical and therapeutic implications.