Cyanobacteria Extract Functions as a Molecular Tool for Neurologic Investigations

Investigators from the University of California, San Diego (UCSD; La Jolla, USA) and Creighton University (Omaha, NE, USA) analyzed the compound in their laboratories and determined that it was a depsipeptide. This is a rather unusual chemical structure where one or more of the peptide's amide (-CONHR-) bonds are replaced by ester (COOR) bonds.

Results from tests of the biologic activity of hoiamide A were published in the August 28, 2009, online edition of the journal Chemistry & Biology. The authors reported that in addition to having modest cytotoxicity to cancer cells, pure hoiamide A affected the neurologic system by potently inhibiting batrachotoxin binding to voltage-gated sodium channels and activating sodium influx in neocortical neurons. Batrachotoxin is a nerve poison where neurological function depends on depolarization of nerve and muscle fibers due to increased sodium ion permeability of the excitable cell membrane. Lipid-soluble toxins such as batrachotoxin act directly on sodium ion channels involved in action potential generation and by modifying both their ion selectivity and voltage sensitivity.

"Classically, what we know about the workings of the human nervous system has come largely from studies of different toxins on the function of model systems, such as in this case, the action of hoiamide A on nerve cells in petri dish cultures,” said senior author Dr. William Gerwick, professor of oceanography and pharmaceutical sciences at UCSD. "The toxins serve as molecular tools for manipulating cells at an extremely microscopic scale. Ultimately, by understanding how neurons work at this detailed level, and having a set of tools such as hoiamide A, we can envision the development of new, more effective treatments for such diverse conditions as epilepsy, pain control, and memory and cognition enhancement. The natural world still has many valuable molecules left for us to discover and hopefully develop into new classes of medicines.”

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University of California, San Diego
Creighton University