Neuronal lesioning with axonally transported toxins

Axonally transported toxins can be used to make selective lesions of the ne rvous system. Collectively, these techniques are termed 'molecular neurosur gery' because they exploit the surface molecular identity of neurons to sel ectively destroy specific types of neurons. Suicide transport, is anatomica lly selective but not type-selective. The most widely used suicide transpor t agents are the toxic lectins (ricin, volkensin) and the immunotoxin, OX7- saporin. The toxic lectins and saporin are ribosome inactivating proteins t hat irreversibly inhibit protein synthesis. The toxic lectins have binding subunits but saporin requires a targeting vector to gain entrance into cell s. Immunolesioning uses monoclonal anti-neuronal antibodies to deliver sapo rin selectively into neurons that express a particular target surface antig en. Neuropeptide-saporin conjugates selectively destroy neurons expressing the appropriate peptide receptors. Notable experimental uses of these agent s include analysis of the function of the cholinergic basal forebrain (192- saporin) and pain research (anti-DBH-saporin, substance P-saporin). It is l ikely that more immunolesioning and neuropeptide-toxin conjugates will be d eveloped in the near future. (C) 2000 Published by Elsevier Science B.V.