Science Editor

Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.

Chemists at the Scripps Research Institute in La Jolla, Calif., have expanded a previous finding that a chemical called nornicotine modifies proteins that misfold and form the fibril amyloid plaques that are abundant in the brains of patients with Alzheimer's disease (AD). This finding at first glance seems to reinforce a long-held but unproved finding that cigarette smoking benefits AD.

Their paper in the current Proceedings of the National Academy of Sciences (PNAS) is titled "Glycation of the amyloid b by a nicotine metabolite: A potentially fortuitous chemical dynamic between smoking and Alzheimer's disease." An earlier PNAS paper released Oct. 30, 2002, in this line of research by the same authors at Scripps bears the crisper title: "A previously undescribed chemical link between smoking and metabolic disease."

The current paper makes the point that nornicotine, a major metabolite of nicotine in the central nervous system, is naturally present as the primary alkaloid in tobacco. The authors demonstrate that nornicotine combined with glucose - a common sugar found in the body - attaches itself covalently (that is, permanently) to amino acids on the surface of amyloid beta protein and prevents them from misfolding and forming senile plaque fibrils.

Whether or not this effect might ameliorate AD is not known, the paper notes. It adds that fibrils of aggregated amyloid beta proteins are present in the brains of Alzheimer's patients, and that this aggregation is an accepted primary pathological marker for AD. These plaque-forming fibrils may be causing the disease or just acting as a bystander protein. "Nornicotine," observed the paper's senior author, "seems to prevent their aggregation and, thus, could potentially impact the onset of Alzheimer's disease.

"In any case," he warns, "these conclusions do not necessarily mean that smoking prevents AD, and this research gives no indication that smoking is beneficial to your general health. There are a vast number of toxic components in tobacco smoke. Nornicotine is toxic and addictive, and is not likely to make a good therapeutic. Nevertheless," he continued, "the research is promising because it demonstrates how one small molecule can cause a chemical interaction that may alter a mechanism important in Alzheimer's disease. This could lead to the development of small molecules similar to nornicotine that are not toxic but could behave in a similar fashion - prevent the aggregation of amyloid beta protein and perhaps treat AD."

Rice, World's Top Food Crop, Sequenced, Netting 3,471 Genes, 22,422,563 Bp On Chromosome 10

Among the dozens of genomic sequences published each year, only two organisms have achieved symbolic status - that of humans (Homo sapiens) and of rice (Oryza sativa). Rice is the world's most important food crop, and a model for cereal research. It's been cultivated for more than 9,000 years, and is a major food staple, providing more than half the daily calories for about a third of the planet's human population.

Rice is considered a model system for plant biology, largely because of its compact genome (430 myoglobin) and evolutionary relationships with other large genome grains such as sorgum (730 Mb), maize (2,500 Mb), barley (5,000 Mb) and wheat (15,000 Mb).

An international effort is under way to publish the complete gene sequence of rice by next year. Work on chromosome 10 is now finished, according to a report in Science dated June 6, 2003, and titled "In-depth view of structure, activity and evolution of rice chromosome 10." Its authors are the myriad member scientists of the international Rice Chromosome 10 Sequencing Consortium. They have identified 3,471 genes on chromosome 10 - more than twice as many as the prior graft sequences - and a pseudomolecule representing 22,422,563 base pairs of unique, non-overlapping of chromosome 10 sequence, derived from 210 clones, was constructed. The completed sequences of all 12 rice chromosomes will have a total of 430 million DNA base pairs. (See BioWorld Today, April 5, 2002.)

A commentary accompanying the Science article is titled "Surprises inside a green grass genome." It observes that the rice genome, along with those to be produced by several other crop and forest plant projects, "will create opportunities for a greater understanding of higher plant biology and ecology that is necessary to guarantee our food supply and protect our biodiversity."

Morning-After, Pregnancy-Ending RU486 Also Rescues Brain Cells From Injury, Psychosis

RU486, the same "morning-after" synthetic chemical used to terminate pregnancies, also may help protect brain cells from the effects of nerve damage. Also known as mifeprestone, RU486 appears to extend the life of certain brain cells, reports a paper in the Proceedings of the National Academy of Sciences released June 3, 2003. Its title: "Mifeprestone (RU486) protects Purkinje cells from cell death in organotypic slice cultures of postnatal rat and mouse cerebellum." Its coauthors are scientists at INSERM, France's National Institute of Health and Medical Research.

Their findings suggest that mifeprestone also protects brain cells during traumatic brain injury, and improves symptoms in patients with psychotic depression. The drug binds strongly to steroid receptors, implying a mechanism by which it may prevent apoptosis.

To determine mifeprestone's mode of action, the French authors tried to mimic or prevent the drug's action. They used cerebellar Purkinje cells as a model isolated from newborn mice. Their brain cells underwent programmed cell death in tissue culture. In addition, brain cells isolated from mice with an inactive mutant version of either the progesterone or glucocorticoid steroid receptor still were rescued by the addition of mifeprestone.

Further experiments showed that the drug's effects were not due to antioxidant activity, suggesting that it acts through a novel pathway to prevent brain cell death. That protective effect of RU486, the co-authors observed, may offer a future treatment for selected neurodegenerative diseases.