Figure 1.

Schematic model of the mechanism relating HDAC1 to impaired axonal transport in response to glutamate and cytokines. In physiological conditions, cargos are transported by motor proteins along microtubules. However when neurons are exposed to inflammatory stimuli such as glutamate and TNFα, activated glutamate receptors uptake calcium into the neurons and induce HDAC1 export in a CRM1-dependent manner. In the cytoplasm, HDAC1 competes with the adaptor proteins for binding to the motor proteins. In these conditions, the cargo is unable to form functional interactions with the motors and therefore axonal transport is blocked.