Microtubules are the main cytoskeleton component responsible for the polarity of the axon. Microtubule minus end defined by the α-tubulin sideis located proximally, nearer to the soma, whereas the the plus end is defined by β-tubulin side, which is located distally, closer to the nerve terminal(6). The polarity of microtubules and consequently of the axon is given by this orientation and therefore directs motors protein to undergo anterograde (toward the plus end) or retrograde (toward the minus end) transport (Figure 1). Conversely, in dendrites, microtubules are found in mixed polarity. Microtubules are essential for axonal transport and any changes in their components may lead to impaired axonal transport under diabetes.

Diabetic neuropathy involves a decrease in axon caliber, axonal transport impairment, and a reduced capacity of nerve regeneration, which are dependent on axonal cytoskeleton integrity for proper nerve function (4). Reduced synthesis of tubulin mRNA and an elevated non-enzymatic glycation of peripheral nerve tubulin was described. Particularly, it was demonstrated that after eight weeks of diabetes T alpha 1 alpha-tubulin mRNA is reduced in streptozotocin (STZ)-induced diabetic rats (7), and an increase in tubulin glycation was detected in the sciatic nerve of STZ-induced diabetic rats after two weeks of diabetes duration, which may contribute to axonal transport abnormalities by impairment of microtubule function (8, 9). Brain tubulin is also glycated in early experimental diabetes, consequently affecting its ability to form microtubules (10). Nevertheless, this finding was not replicated in subsequent studies, where it was demonstrated that glycation was not associated with inhibition of microtubule assembly (8, 11). In the sural nerves of diabetic patients it was detected an increase in advanced glycation end products accumulation in cytoskeletal proteins (12), suggesting that axonal cytoskeletal proteins glycation may play a role in axonal degeneration polyneuropathy in diabe