CX3CR1 links Toxic Tau accumulation to microglial inflammation

CX3CR1 is a large cytokine protein. The only known member of the chemokine receptor family, it is a receptor for the novel transmembrane protein fractalkine (CX3CL1). We at Novus Biologicals have an antibody database of 11 CX3CR1/CX3CL1 antibody products. Recently, researchers at the Cleveland Clinic Foundation, Ohio, used these antibodies to show a link between neurodegenerative disorders such as Alzheimer’s disease, and the immune system.

CX3CR1 is a mediator of leukocyte adhesion and migration, which require both chemotactic and cellular adhesion factors. Fractalkine is expressed on endothelial cells activated by tumour necrosis factor-a and interleukin-1, while the CX3CR1 receptor is expressed on a variety of cells, including monocytes, natural killer (NK) cells, microglia and, to a lesser extent, cytotoxic T cells.

Fractalkine/CX3CR1 binding mediates chemotaxis and also cell adhesion, in the absence of other suitable substrates. It has also been shown to act as an important signalling pathway for neuron and microglia communication.

In 2001, H. Umehara and T. Imai showed fractalkine-expressing endothelial cells underwent increased osmotic lysis following fractalkine-mediated NK cell activation. This suggested a pathogenic role, since endothelial cells are at the forefront of immunological attack. CX3CR1 was recently found to be a co-receptor tor viral infection and envelope fusion of HIV-1 and HIV-2. It has also been implicated in metastasis of tumours.

In 2010, Lamb et al studied the signalling pathway of CX3CL1 and CX3CR1in neurons, to see if there was a link between MAPT (microtubule associated protein tau) aggregation, or taupathy, and microglial inflammation as a result of CX3CR1/Fractalkine signalling. A combination of animal models, cultured cell lines and antibody assays showed microglial inflammation triggered MAPT phosphorylation and aggregation in all the systems tested.

The study gave invaluable information on the CX3CL1/CX3CR1 signalling pathway, and suggested CX3CL1/CX3CR1 antibodies could be of use in developing novel therapies against taupathic disorders.

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