Science Zeroes In on New Alzheimer's Drug Target

May 7 -- WEDNESDAY, May 6 (HealthDay News) -- Drugs that control the "wrapping" of certain DNA have brought back learning and memory to mice stricken with an Alzheimer's-like disease -- and scientists now believe they know how.

The finding, published in the May 7 issue of Nature, suggests a novel therapeutic target for Alzheimer's and other diseases that impair learning and memory.

Study lead author Li-Huei Tsai, Picower Professor of Neuroscience at the Massachusetts Institute of Technology, explained that the key player here is an enzyme called histone deacetylase-2 (HDAC2). HDAC2's job in the cell is to control how tightly chromosomal DNA wraps around protein spools called histones.

Just how tightly or loose that binding is appears to influence cognition in mice, the researchers said.

Overexpress the protein and the mice have trouble learning -- for instance, to work their way through a water maze. But if HDAC2 is eliminated altogether, or if its activity is blunted with chemical inhibitors, the mouse's ability to learn improves, the team found.

The new findings help explain the results of an earlier study, also by Tsai's group. It showed that a nonspecific HDAC inhibitor-type drug could improve cognitive function in a mouse model of Alzheimer's disease.

"To the degree that more [synaptic plasticity] is better, then something that opposes HDAC2 function would be expected to improve memory or cognition -- or at least improve the ability of an animal to navigate a water maze," said Dr. Lon Schneider, professor of psychiatry, neurology, and gerontology at the University of Southern California. He was not involved in the new study.

HDACs perform a critical role in mammalian cells, including humans. The genomic material that is found within every cell does not exist as free-floating, naked molecules. Instead, it is carefully compacted into a structure called chromatin, in which DNA is wrapped around histone spools. This makes it easier for the cell to manipulate the DNA -- for instance, to move it during cell division. But there's a catch: The more tightly wound the DNA is, the less accessible it is to the proteins that read out its instructions.