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UCSD Researchers ID Peptides That Bind to
Alzheimer’s Plaques From Eurekalert (American Association for the
Advancement of Science) September 8, 2003 Two short protein segments,
called peptides, have been identified by researchers at the University of
California, San Diego (UCSD) School of Medicine, for their ability to
recognize and bind to beta-amyloid-containing plaques that accumulate
abnormally in the brains of Alzheimer’s disease patients, providing a
possible “Trojan horse” mechanism to diagnose and treat the disorder.
In studies published in the
September issue of the journal Neurobiology of Disease (published
online Aug. 27, 2003), Martin and colleagues found that natural and
synthetic versions of the peptides attach themselves to the abnormal
plaque, while ignoring normal brain tissue. Although past research has
identified larger non-antibody and antibody proteins and small organic
molecules that can bind to the amyloid plaques, the UCSD team said the
newly discovered peptides may be a better choice for diagnosis and
treatment. Smaller in size than previously identified proteins, the
peptides may more easily cross the blood-brain barrier. In addition, some
of the previously identified organic molecules could cause toxic side
effects if given to people. The scientists used a
laboratory technique called phage peptide display to identify the two
peptide sequences from a starting library of 50 million peptide sequences.
These peptides were engineered to be exposed on the surface of bacteria by
infecting the bacteria with bacteriophage (a bacterial virus). The
peptide-expressing bacteria were then used to select for peptide sequences
that bound amyloid plaques. An analysis of the bacteriophage showed that
only the two peptides were able to seek out and bind to abnormal beta-amyloid. “It is striking that we found
only two peptide sequences, and that they were very similar in structure
to one another,” Martin said. “This suggests that if other sequences
do exist, they would most likely be variations on the structures we have
already identified.” He added that the UCSD team
sees several potential applications for the peptides. First, they could be
coupled to molecules designed to inhibit the toxicity of beta-amyloid
plaques. The peptides might also be coupled to substances that stimulate
the breakdown of plaques, or inhibit them from forming. A final
application would be coupling the peptides to other markers that would
highlight the abnormal plaque in imaging diagnostic tests. Currently,
Alzheimer’s disease is diagnosed by cognitive tests involving patient
interview, and a conclusive diagnosis requires postmortem analysis of the
brain itself. In addition to Martin, authors
of the study included Christine Kang, staff research associate, and
Vianney Jayasinha, an undergraduate student, in the UCSD Department of
Neurosciences. The study was funded by the National Institutes of Health. Copyright
© 2002 Global Action on Aging
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