Enzyme counters Alzheimer's-like snarls. (Untangling the Brain).An enzyme prevents brain cells in aging mice from developing knots of proteins resembling those that are a hallmark 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. , scientists report. Known as Pin1, the enzyme could form the basis of new treatments for the memory-stealing disorder.
In 1995, Kun Ping Lu LU Ping (Chinese: 路平; Pinyin: Píng Lù), born in Kaohsiung in 1953, writes under the pen name "PING Lu. of Beth Israel Deaconess Medical Center Both an international and regional referral center, Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts is a major teaching hospital of Harvard Medical School. It was formed out of the 1996 merger of Beth Israel Hospital (founded in 1916) and in Boston and Tony Hunter of the Salk Institute for Biological Studies The Salk Institute for Biological Studies is an independent, non-profit, scientific research laboratory located in La Jolla, California. It was founded in 1960 by Jonas Salk, M.D., the developer of the polio vaccine. in La Jolla La Jolla (lə hoi`yə), on the Pacific Ocean, S Calif., an uninc. district within the confines of San Diego; founded 1869. The beautiful ocean beaches, in particular La Jolla shores and Black's Beach, and sea-washed caves attract visitors and , Calif., discovered Pin1. They subsequently showed that it interacts with a protein called tau, an important component of one of the two brain lesions seen in Alzheimer's disease. Known as tangles, these snarls of tau filaments turn up inside nerve cells. In contrast, the other lesion consists of an abnormal buildup outside nerve cells of a protein fragment known as beta-amyloid.
Most neuroscientists favor the hypothesis that beta-amyloid triggers the brain-cell loss in Alzheimer's disease, but some argue that tau is equally, if not more, important. Tau protein normally shapes a cell's interior skeleton, but in Alzheimer's disease, molecular tags called phosphates get added to tau. This embellishment seems to promote tangle formation.
Lu, Hunter, and their colleagues had shown that Pin1 binds to tau overloaded with phosphates. This alters the protein's shape in such a way that those tags get shed. "It's important for restoring the function of tau," says Lu.
This finding and others persuaded Lu that Pin1 can protect brain cells from the ravages rav·age
v. rav·aged, rav·ag·ing, rav·ages
1. To bring heavy destruction on; devastate: A tornado ravaged the town.
2. of tangles. Some investigators, however, interpreted the data differently, arguing that the enzyme actually contributes to tangle formation.
In the July 31 Nature, Lu, Hunter, and their colleagues report that mice with an inactive Pin1 gene suffer nerve cell loss in the spinal cord spinal cord, the part of the nervous system occupying the hollow interior (vertebral canal) of the series of vertebrae that form the spinal column, technically known as the vertebral column. and brain as the animals age. The mice show decreasing mobility and general loss of muscle coordination.
A close examination of the brains of the mice revealed that select regions exhibited nerve cell degeneration. In those areas, tau proteins were studded with phosphates and were tangled. Other researchers have induced tangle formation in mice by giving the rodents extra copies of the human tau gene but not by inactivating a gene, says Lu.
"This is the first demonstration that mouse tau can form structures similar to what we see in human brain," adds Mark Smith of Case Western Reserve University in Cleveland. "It will be a useful model to clarify the connection between tau and neurodegeneration."
While studying preserved brain tissue from people who had Alzheimer's disease, Lu and his colleagues also found that regions with the highest concentrations of Pin1 had the lowest percentages of nerve cells with tangles. Moreover, in healthy brains, the highest concentrations of the enzyme appear in areas that Alzheimer's disease doesn't normally destroy, the scientists report.
The animal and human data together create a "strong case" that Pin1 protects against Alzheimer's disease, says D. Stephen Snyder of the National Institute on Aging The National Institute on Aging is a division of the U.S. National Institutes of Health, located in Bethesda, Maryland.
Formed in 1974, NIA's mission is to improve the health and well-being of older Americans through research. It is the primary U.S. in Bethesda, Md.
Smith isn't quite as convinced, noting that the mutant mice experience nerve cell loss in brain regions different from those afflicted af·flict
tr.v. af·flict·ed, af·flict·ing, af·flicts
To inflict grievous physical or mental suffering on.
[Middle English afflighten, from afflight, by Alzheimer's disease. "I'm not sure this [new study] shows the role of Pin1 in Alzheimer's disease as much as it shows a role in neurodegeneration," he says.