Neuronal lesioning with axonally transported toxins.
Axonally transported toxins can be used to make selective lesions of the nervous system. Collectively, these techniques are termed 'molecular neurosurgery' because they exploit the surface molecular identity of neurons to selectively destroy specific types of neurons. Suicide transport, is anatomically selective but not type-selective. The most widely used suicide transport agents are the toxic lectins (ricin, volkensin) and the immunotoxin, OX7-saporin. The toxic lectins and saporin are ribosome inactivating proteins that irreversibly inhibit protein synthesis. The toxic lectins have binding subunits but saporin requires a targeting vector to gain entrance into cells. Immunolesioning uses monoclonal anti-neuronal antibodies to deliver saporin selectively into neurons that express a particular target surface antigen. Neuropeptide-saporin conjugates selectively destroy neurons expressing the appropriate peptide receptors. Notable experimental uses of these agents include analysis of the function of the cholinergic basal forebrain (192-saporin) and pain research (anti-DBH-saporin, substance P-saporin). It is likely that more immunolesioning and neuropeptide-toxin conjugates will be developed in the near future.
Wiley
R G
RG
Departments of Neurology and Pharmacology, Vanderbilt University, VAMC Nashville, TN 37212-2637, USA. ronald.g.wiley@vanderbilt.edu
Kline IV
R H
RH
D000818:Animals; D000911:Antibodies, Monoclonal; D001370:Axonal Transport / Q000187:drug effects* / Q000502:physiology; D019771:Axotomy / Q000379:methods*; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006023:Glycoproteins; D018796:Immunoconjugates; D000922:Immunotoxins / Q000633:toxicity; D009699:N-Glycosyl Hydrolases; D009410:Nerve Degeneration / Q000139:chemically induced*; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009479:Neuropeptides / Q000633:toxicity; D009498:Neurotoxins / Q000633:toxicity*; D037121:Plant Lectins; D010940:Plant Proteins / Q000633:toxicity; D054789:Ribosome Inactivating Proteins, Type 1; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin / Q000633:toxicity; D000076985:Saporins
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D018796:Immunoconjugates; D000922:Immunotoxins; D009479:Neuropeptides; D009498:Neurotoxins; C085346:OX7-saporin; D037121:Plant Lectins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin; C049134:volkensin; D009699:N-Glycosyl Hydrolases; D000076985:Saporins