Alzheimer's disease enzyme identified.
Researchers at the University of Texas Southwestern Medical Center in Dallas have defined a key step in the production of beta-amyloid, a short protein that is thought to be responsible for the development of Alzheimer's disease Alzheimer's disease (ăls`hī'mərz, ôls–), degenerative disease of nerve cells in the cerebral cortex that leads to atrophy of the brain and senile dementia. .
In Alzheimer's disease, too much beta-amyloid is produced by an enzyme that has many other essential roles. As a result, simply blocking the whole enzyme knocks out many of its other functions, which is fatal to the organism.
Using cultured human cells, as well as test-tube assays, university researchers singled out how just one portion of the enzyme, a protein called nicastrin, is involved in the pathway that produces beta-amyloid, thereby leading to Alzheimer's disease.
"The work provides an attractive potential strategy for developing treatment for Alzheimer's disease," said Dr. Gang Yu, senior author of the study. The research uncovered an "unprecedented mechanism of biochemistry biochemistry, science concerned chiefly with the chemistry of biological processes; it attempts to utilize the tools and concepts of chemistry, particularly organic and physical chemistry, for elucidation of the living system. ," Dr. Yu said.
Nicastrin is a large protein that is a component of an enzyme called gamma-secretase, which is lodged in the cell's membrane. When it is at the cell surface, nicastrin sticks out into the area outside the cell. It was thought to play a key role in the creation of amyloid-beta, although the exact mechanism was unknown.
Dr. Yu and his colleagues discovered that nicastrin binds to several proteins lodged in the cell's membrane, including one called amyloid precursor protein Amyloid precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. Its primary function is not known, though it has been implicated as a regulator of synapse formation and neural plasticity. , or APP See application.
app - application program . Nicastrin then guides membrane-bound proteins to the active area of gamma-secretase, which then splits the proteins.
APP, for example, is chopped into two parts: amyloid-beta is shipped to the outside of the cell, and another part remains inside. Amyloid-beta forms the plaques seen in the brains of patients with Alzheimer's disease.
Now that nicastrin's function has been ascertained, it opens a way to block just the splitting of APP, leaving all the enzyme's other functions intact. For instance, it may be possible to generate chemical compounds that specifically prevent nicastrin from latching latch
1. A fastening, as for a door or gate, typically consisting of a bar that fits into a notch or slot and is lifted from either side by a lever or string.
2. on to APP. If APP does not attach to nicastrin, APP remains intact and harmless. Meanwhile, nicastrin would be free to bind all the other essential proteins that it works on.
"We want to find a particular way to block the recognition of APP but not the others," he said.
(Source: Cell, August 12, 2005.)