NYC Healthcare News



Microglial inflammation promotes MAPT pathologies

November 24, 2015

In order to examine the link between microglia and tauopathy, Dr. Lamb and colleagues studied a specific signaling pathway through which neurons and microglia communicate, fractalkine (CX3CL1), a chemokine expressed in neurons, and its receptor (CX3CR1) which is expressed exclusively in microglia. Dr. Lamb's group evaluated perturbations of this signaling pathway in several different model systems, including a mouse model of inflammation, a mouse model of tauopathy (hTau) and microglia and neurons grown in the laboratory. They found that microglial inflammation promoted MAPT phosphorylation and aggregation in all of the model systems.

"Importantly, introduction of CX3CR1 deficiency into hTau mice resulted in altered microglial activation, enhanced MAPT phosphorylation and aggregation, as well as behavioral abnormalities," says Dr. Lamb. In addition to documenting the effects of a specific microglial receptor on MAPT pathology, the researchers also gained new insight into specific signaling molecules downstream of the CX3CL1/CX3CR1 interaction. Taken together, the findings reveal a direct link between the activation of microglia and the abnormal phosphorylation and aggregation of MAPT in neurons and suggest potential novel therapeutic strategies for tauopathies.

Source: Cell Press