Fraktalkine

Fraktalkine, or CX3CL1, is a chemokine of the CX3C family. It is unique among chemokines because it exists in two forms: a membrane-anchored protein with a mucin-like stalk that can promote cell adhesion, and a soluble chemokine produced when the extracellular portion is shed by metalloproteases such as ADAM10 and ADAM17. The CX3CL1 gene encodes the protein and is widely expressed, with prominent expression by neurons in the central nervous system and by endothelial cells in peripheral tissues.

Fraktalkine signals through its receptor CX3CR1, a G protein-coupled receptor expressed on monocytes, natural killer cells, subsets of T cells, and microglia. The membrane-bound form mediates adhesion of CX3CR1-expressing cells to fractalkine-bearing surfaces, whereas the soluble form acts as a chemoattractant and activator.

In the CNS, neuron-derived fractalkine participates in neuron-microglia communication and helps regulate microglial activation and surveillance of the neural environment; in peripheral tissues it directs leukocyte trafficking during inflammation. The axis can have pro- or anti-inflammatory effects depending on context and cell type.

Dysregulation of CX3CL1–CX3CR1 signaling has been associated with several diseases. In neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, altered fractalkine signaling may influence microglial activation and disease progression. It is also studied in models of neuropathic pain and inflammatory diseases. Therapeutic strategies targeting this axis include CX3CR1 antagonists or agents that modify shedding, aiming to modulate microglial activation or leukocyte recruitment while balancing host defense.