Protection for neurons

Research at UFRJ indicates therapeutic strategies for Alzheimer's disease

The research of the biochemist Dr. Sérgio Teixeira Ferreira, of the Federal University of Rio de Janeiro (UFRJ), is opening the way for the development of medicines that will act against Alzheimer’s disease, of which, at the moment, only the symptoms are combated. In an article in the March on line issue of The FASEB Journal, Dr. Ferreira describes the results of experiments done with two organic compounds, 2,4-dinitrophenol or DNP and 3-nitrophenol or NP. Both of them, in low concentration, cause the “complete dissociation of the fibers of beta-amyloid”, a peptide (a fragment of protein) that has a central role in the advancement of the disease. It forms plates that intoxicate the neurons of the brain and lead to the loss of memory and sanity.

The research was done initially in test tubes with the neurons of rats, and the two substances were able to block the cell death induced by beta-amyloid (74% to 65% of survival with DNP and NP respectively). Afterwards, it was confirmed on living organisms that the two substances can hinder the formation of peptide plates on the brain of adult rats.

The direct use of DNP and NP is not being considered, but they can serve as chemical models, or as they say, leader compounds, in the development of effective and safe drugs. “These substances are proving to be a type of antidote against the toxic effects of beta-amyloid on the neurons.” said Dr. Ferreira, who has filed the registration for the patent for the process which he has developed in Brazil and in the United States. Preliminary data indicate that the two compounds stimulate the formation of branches of the neurons (axons and dendrites). In this way the neurons become more robust, more connected between themselves and more resistant to the action of beta-amyloid.

In another article, also published in March in Neuroscience Letters, Dr. Ferreira and his team showed that the toxic effect of beta-amyloid could be restrained by the antagonists (molecules that annul the action of others) of glutamate, one of the main components of proteins. In the nervous system, glutamate acts as a neurotransmitter, conducting information of one cell to another.

“By blocking the action of glutamate, we also block the action of beta-amyloid.” says Dr. Ferreira. The antagonists used (MK801, DNQX and AIDA) link themselves to the specific cellular receptors for glutamate, which remains inactive. Thus, it has been shown that the partial control of the receptors of glutamate could be another way towards the development of new medicines.

The spreading of Alzheimer’s disease enhances the importance of this work. Initially diagnosed as mental confusion and forgetfulness of recent events, this is the most common form of insanity among the aged, hitting between 5 and 10% of the population older than 65 years of age.