Potent new compound from blue-green algae may help treat, elucidate nerve disorders

December 18, 2000

Click here for abstract.

HONOLULU, Dec. 19 - Amid a growing list of biologically useful chemicals from the sea, a newly discovered compound - kalkitoxin - stands out for its potential to help researchers understand nerve function, which could someday lead to new treatments for pain, epilepsy and possibly stroke. The finding was reported here today at the 2000 International Chemical Congress of Pacific Basin Societies.

The weeklong scientific meeting, held once every five years, is hosted by the American Chemical Society, in conjunction with its counterparts in Australia, Canada, Japan and New Zealand.

Lead investigator William Gerwick, Ph.D., a pharmacy professor at Oregon State University in Corvallis, says the neurotoxin - a metabolite in cyanobacteria - is fundamentally new in both structure and potency.

"What we've found is a spectacularly potent neurotoxin, meaning kalkitoxin can kill neurons," explained Gerwick. "And when a compound is very toxic, it's working by a very specific mechanism." He and his collaborators hope to use that mechanism "to dissect neurochemical pathways and to understand how drugs affect them," he said.

Their discovery began "in an absolutely beautiful bay" of the Caribbean island of Curacao, near Venezuela, Gerwick said. "In 1994, we found a collection of cyanobacteria growing like hairs off the sea floor. We brought several liters of it back to Oregon for testing." Marine cyanobacteria, also called blue-green algae, are most familiar to many people as "pond scum."

Back in the laboratory, Gerwick's team ground up samples of the simple plant and tested extracts on brine shrimp and fish. One extract proved toxic even in concentrations of parts per billion. The researchers named the as-yet-mysterious compound after the island's Kalki Bay and set to work tracking down its structure.

The project proved to be a challenge for the next several years. Kalkitoxin's three-dimensional structure "turned out to be particularly tricky," said Gerwick. "It turned out to have five stereo centers, and ones that are hard to reach."

Like hands, molecules can be identical in chemical composition - but the arrangement of their atoms in space can make them mirror images of each other. Such sites, or stereo centers, within a biologically active molecule often form the finely crafted pockets or arms with which it latches on to enzymes, nerve-cell receptors and other molecules in the body.

While kalkitoxin's purpose in cyanobacteria is still uncertain, said Gerwick, its target in animals appears to be sodium-ion channels. These pores within the membranes of neurons are voltage gates, he explained, the primary means by which neurons build up electrical charge. Kalkitoxin appears to block sodium channels, preventing the nerve cells from firing off their electrical signals.

Interestingly, drugs such as topiramate help suppress epileptic attacks largely by blocking sodium channels. Such painkillers as lidocaine are sodium-channel blockers as well. "These disorders, including neurodegenerative diseases, could be treated by selectively activating and blocking sodium channels," said Gerwick. "So even if kalkitoxin doesn't become a useful pharmaceutical itself, it's a valuable tool to understanding how the channels work and how disease and drugs affect them."

More than 8,000 research papers will be presented during this year's International Chemical Congress, which is sponsored jointly by the American Chemical Society, the Chemical Society of Japan, the Canadian Society of Chemistry, the Royal Australian Chemical Institute and the New Zealand Institute of Chemistry.
-end-
The paper on this research, ORGN 1774, will be presented at 8:05 a.m., Tuesday, Dec. 19, at the Hilton Hawaiian Village, Tapa Ballroom III, Tapa Conference Center, during the "Paul J. Scheuer Symposium: Celebrating a Half-Century of Research at the University of Hawaii," which is part of a larger symposium, "Marine Natural Products Chemistry."

William Gerwick is a professor in the College of Pharmacy at Oregon State University in Corvallis, Ore.

American Chemical Society

Related Neurons Articles from Brightsurf:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.

Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.

A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.

Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.

Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.

Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.

The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.

Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.

How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.

Read More: Neurons News and Neurons Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.