Mechanism of Action of Presynaptic Neurotoxins
Abstract
The fundamental mechanisms involved in the action of the Clostridial neurotoxins are discussed. A neuroblastoma cell line, N18 RE105 that has a large number of high affinity tetanus toxin receptors analogous to those found in normal brain has been identified. Complex glycolipids, known as ganliosides, were found in these cells and most likely function as the physiological receptor for tetanus toxin. These cells were also used to identify a rapid temperature dependent uptake of toxin into the cells. This high affinity uptake mechanism is dependent upon the metabolic energy of neuronal cells. This internalization is almost certainly involved in the intoxication process and explains why once exposed to toxin it is not possible to save patients with antibody treatment. A number of compounds have been screened to try to inhibit this internalization, and one, cytochalasin B is very promising, In further studies we have identified another cell line, PC12, that also binds tetanus toxin with high affinity. We have found that it is necessary to differentiate these cells with nerve growth factor to get significant binding. These cells should be a valuable system to use in screening assays for Clostridial neurotoxins.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1986
- Accession Number
- ADA176364
Entities
People
- Terry B. Rogers
Organizations
- University of Maryland School of Medicine