CX3CL1 Regulation of Gliosis in Neuroinflammatory and Neuroprotective Processes

Among the different chemokines, C-X3-C motif chemokine ligand 1 or CX3CL1, also named fractalkine, is one of the most interesting due to its characteristics, including its unique structure, not shared by any other chemokine, and its ability to function both in a membrane-bound form and in a soluble form, among others. However, undoubtedly, its most relevant characteristic from the neuroscientific point of view is its role as a messenger used by neurons to communicate with microglia. The study of the interaction between both cell types and the key role that CX3CL1 seems to play has facilitated the identification of CX3CL1 as a crucial modulator of microglial activation and a promising target in the fight against neuroinflammation. As a result, numerous studies have contributed to elucidate the involvement of CX3CL1 and its specific receptor CCX3CR1 in the progression of different neuroinflammatory and neurodegenerative processes, with Alzheimer's and Parkinson's diseases being the most studied ones. However, the different animal and cellular models used to reproduce the pathological conditions to be analyzed, as well as the difficulties inherent to studies performed on human samples, have hindered the collection of compatible results in many cases. In this review, we summarize some of the most relevant data describing the alterations found for the CX3CL1/CX3CR1 signaling axis in different neurodegenerative conditions in which neuroinflammation is known to play a relevant role.