Unit

UNIT 1.7 Targeted Toxins

  1. Ronald G. Wiley1,
  2. Douglas A. Lappi2

Published Online: 1 MAY 2001

DOI: 10.1002/0471142301.ns0107s14

Current Protocols in Neuroscience

Current Protocols in Neuroscience

How to Cite

Wiley, R. G. and Lappi, D. A. 2001. Targeted Toxins. Current Protocols in Neuroscience. 14:1.7:1.7.1–1.7.11.

Author Information

  1. 1

    Veterans Affairs Medical Center, Nashville, Tennessee

  2. 2

    Advanced Targeting Systems, San Diego, California

Publication History

  1. Published Online: 1 MAY 2001
  2. Published Print: FEB 2001

Abstract

Molecular neurosurgery can be used to make selective neural lesions by targeting cytotoxins to specific populations of neurons based on their common expression of a particular surface molecule. The targeted toxins employed in this unit consist of a targeting moiety (vector) and an effector moiety (cytotoxin). In all cases discussed in this unit, the cytotoxic moiety is an enzyme that catalytically inactivates the large ribosomal subunit, irreversibly inhibiting protein synthesis and resulting in cell death. These toxins appear to kill in an all-or-none fashion, indicating that one molecule of free cytotoxin in the cytoplasm of a cell is sufficient to kill the cell. Three general molecular neurosurgery protocols are presented in this unit. The first describes suicide transport, which refers to the use of targeted toxins to make anatomically restricted lesions based on retrograde axonal transport of the toxin. The second involves immunolesioning and uses anti-neuronal immunotoxins to make type-selective and anatomically restricted lesions. The final protocol uses neuropeptide-toxin conjugates to selectively destroy neurons expressing the receptor for the specific neuropeptide.