Brain
Bounceback (video) - About 750,000 Americans suffer a stroke
each year. In many cases, their ability to understand and use
language is severely impaired. Now scientists can see why this
ability is not lost for good. (10/18/02)
Mixed
Signals (video) - Are current drugs for Parkinson’s
disease ineffective? New research shows that mixed signals in
Parkinson’s patients’ brains means a cure could be
farther away than previously hoped. (10/8/02)
Elsewhere on the web
Netting
the aggregate
The
State of HD Research
New
Release: Findings aid understanding of neurodegenerative diseases
Huntington
Society of Canada
Just like traffic jams clog a city’s roads, sometimes proteins in our
body break down and clog up our cells.
As this ScienCentral News video reports, when this happens in our brain, it
leads to devastating illnesses.
Protein Misfolding
Proteins, the basic components of all living cells, are made up of different
combinations of amino acids. In order to carry out their biochemical function,
each protein must first take on a particular shape, which happens when the
amino acids fold into place. This delicate process of protein folding is critical,
and when the amino acids do not fold correctly (i.e. "misfold"),
the misshapen proteins form clumps, called aggregates, within the cell. These
aggregates then start to attract other healthy proteins that are essential
for cell function, which in turn bend and stop working. As this process continues,
cells shut down and die, and this can lead to devastating neurodegenerative
diseases like Alzheimer’s, new variant Creutzfeldt-Jakob Disease (the
human form of Mad Cow Disease), and Huntington’s
Disease, to name a few.
Richard
Morimoto, professor of biochemistry at Northwestern University, says his
laboratory “has focused on the question of whether our cells contain
other good proteins that are present to prevent disease-causing proteins such
as in Huntington’s.”
Good proteins to the rescue
Morimoto’s team at Northwestern studied molecular
chaperones, another class of proteins that are present in all cells that
seem to prevent misfolding of proteins. While studying aggregates in Huntington’s
patients, Morimoto, lead author of the study published in the October issue
of Nature Cell
Biology, says they noticed that, “a chaperone recognizes an abnormal
protein, binds to that protein and in doing so allows that bad protein to
change and perhaps adopt its normal function.”
Morimoto says that, “molecular chaperons, by binding to these aggregates
that appear in Huntington’s cells, are causing the release of good proteins
that would otherwise be trapped irreversibly in the aggregate.”
The scientists were able to observe all of this in real time by using a technique
called dynamic microscopy. With a high-powered microscope they could visualize
and record the cells in action as the different proteins interacted with the
Huntington’s aggregates.
Says Morimoto, “it’s like the comparison between a still photograph
versus a movie. In a still photograph you get a sense of what event might
have occurred but no sense of how anything got there or how anything else
will change.” Likewise in Huntington’s, Morimoto believes, this
technique allowed them to see that there are some proteins that are irreversibly
brought into the aggregates while others were seen going into the aggregate
and releasing from the aggregate very rapidly.
“This is exciting”, Morimoto says, “because it suggests that
the aggregate itself in Huntington’s is not a permanent structure that’s
irreversible. It means that proteins by coming and going, in particular the
chaperones, provides a hint to us for how we might move to the next step.
That is, design drugs or molecules that enhance the removal of proteins from
the aggregates,” and allow the cells to function better. The study thus
provides a tool for screening and identifying such new and effective drugs.
The research was supported by the National
Institutes of Health, the Huntington’s
Disease Society of America, Coalition for the Cure, the Hereditary
Disease Foundation and the Netherlands Organization for Scientific Research.