Retrograde axonal and transsynaptic transport of macromolecules: physiological and pathophysiological importance

Anterograde and retrograde transport within axons and dendrites of nerve cells represent an integral part of the nerve cell function and biochemistry. A few exogenous macromolecules with most different molecular weights and physico-chemical properties (Nerve Growth Factor, tetanus toxin, cholera toxin, various lectins, antibodies against dopamine-beta-hydroxylase) have been shown to be taken up and transported with the retrograde axonal transport in exceedingly high amounts if compared to most other macromolecules. Specific binding to membrane receptors seems to be the prerequisite for this highly efficient retrograde transport. Upon arrival at the cell body tetanus toxin is able to leave the neuron and to migrate transsynaptically to presynaptic nerve terminals of second-order neurons. For NGF, tetanus toxin and some neurotropic viruses retrograde axonal transport eventually followed by transsynaptic transport may be crucially involved in their mechanism of action. Indirect evidence suggests the existence of a variety of endogenous molecules carrying specific information from the target cell and the nerve terminal to the cell body and eventually transsynaptically into second- or third-order neurons.