knowledge about axonal transport impairment in diabetes, focusing on the various components and mechanisms that control such transport both at peripheral (PNS) and central nervous systems (CNS).

Diabetes mellitus and axonal transport

Role of axonal cytoskeleton

Axonal transport impairments and alterations of the cytoskeleton have been associated with numerous types of peripheral neuropathy and also central neurodegenerative diseases (5). Axonal transport takes place along the cellular cytoskeleton which provides structural support to the neuron. The neuronal cytoskeleton is composed by three major components , namely microtubules, intermediate filaments and microfilaments, which can be affected by diabetes.

Microtubules

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 alph