The cyanobacterium Nostoc 78-12A lives in a cheerless environment in the waste waster lagoons in the USA. Pond scum is what the Americans call the blossoms of these micro-organisms derisively. But the Nostoc 78-12A that lives here is something special. It produces an active substance that may be employed in the treatment of Alzheimer's. Under the guidance of Karl Gademann from the ETH Laboratory of Organic Chemistry and Friedrich Jüttner from the Institute of Plant Biology at the University of Zurich a team of researchers from the two institutions has now succeeded in isolating the new agent called nostocarboline from the cyanobacterium. Paul Becher and Julien Beuchat from the universities of Zurich and Lausanne, respectively, also participated in the study, the results of which were published on 26th December 2005 in the Journal of Natural Products. (1)

Cholinesterase effectively inhibted

In test tube trials, nostocarboline puts the enzyme cholinesterase out of action. Cholinesterase is co-responsible for Alzheimer's, as these proteins break down the neurotransmitter acetylcholine. The brain requires acetylcholine in order to process and store information. When cholinesterase is inhibted the level of acetylcholine increases, which means that the advance of the disease can be slowed down. Various cholinesterase inhibitors are already used in treating initial or medium stages of Alzheimer's. Nostocarboline is the first inhibitor produced from cyanobacteria that can be used to treat the disease. Its effectiveness in vitro tests is comparable to that of the cholinesterase inhibitor galanthamine, which is used in the patent drug Razadyne.

Scientists have known for a long time that nostoc and other cyanobacteria produce many biologically very effective components, which are used in the production of drugs to treat various human diseases. The search for the hormone nostocarboline, however, was like looking for the proverbial needle in a haystack.

Nostoc colony in the retort, the isolated hormone in the test-tube and the print-out of the chemical structure: in the lab of head of study Karl Gademann (Picture: K. Gademann). large

The team had to test hundreds of different cyanobacteria cultures and extract a multitude of substances that then had to be tested for their effectiveness. An immense assembly line effort, but one that finally bore fruit.

Fascinating similarity

Nevertheless, for the head of the study, Karl Gademann, it is not its potential use in the treatment of Alzheimer's that is of imminent interest. Many years will pass until a drug can be brought onto the market based on the newly discovered agent. So far there is no drug that can stop Alzheimer's. Even cholinesterase inhibitors can only slow down the process, not stop it.

However, the analysis of nostocarboline held a surprise in store; with the exception of a single chlorine atom the new active substance is chemically identical to a molecule that the human brain can produce all by itself. "The question now is if too much or too little of this endogenous agent prevents or triggers Alzheimer's," explains Gademann. As the endogenous compound had only recently been discovered, this had not yet been studied. "What is fascinating is that up until now it was generally thought that human beings had been well studied. But humans harbour many compounds whose function are still unknown and that show striking similarities with a molecule from a cyanobacterium," says Gademann.

Suitable as a herbicide

ETH Zurich has patented nostocarboline. Because apart from its potential in medical therapies it also has the makings of a natural pesticide. "Nostoc doesn't produce this matter by pure chance. It protects the cyanobacterium from herbivores such as insects and small crabs or keeps other algae at bay," says the scientist. Nostocarboline inhibits the growth of algae, which makes it a logical candidate for a natural herbicide. In the ocean, for example, it could be employed to combat so-called green tides. In addition the agent is cheap and easy to produce and, as natural matter, it is also biodegradable.