American Society for Cell
Biology,
San Francisco, December, 2002
Deviant gatherings prompt brain disease
Trapped proteins may explain nerve
degeneration.
16 December 2002
HELEN PEARSON
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| Drug companies are looking
for molecules that alter protein shuttling. |
| © GettyImages |
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Many degenerative brain disorders could arise because culprit
proteins are unable to escape the cell's nucleus, gathering data
suggest. Messed up cell transport is increasingly suspected as a
cause of disease.
Proteins encoded by an abnormal string of stutter-like DNA
repeats are involved in a group of neurological conditions
including Huntington's disease. Scientists have scratched their
heads over how the anomaly causes the nerve-cell deterioration
that strikes in middle age.
The proteins have lost the ability to escape the nucleus and
ferry molecules elsewhere in the nerve cells, suggest Ray Truant
of McMaster University in Ontario, Canada, and his colleagues.
"The parallels between the diseases are starting to come
together," he said at this week's American Society for Cell
Biology meeting in San Francisco.
If the theory proves true, the stray proteins might be
redirected, hopes Harry Orr, who studies 'triplet repeat'
diseases at the University of Minnesota in Minneapolis. Some
drug companies are already using high-throughput screens to hunt
for molecules that alter protein shuttling.
Certain control proteins in the cell ensure that others are
shunted correctly. "These pathways might become amenable to
small-molecule drug therapies," suggests Orr.
No way out
Huntington's, an inherited disease that causes cognitive and
movement difficulties, affects 1 in 10,000 people;
spinocerebellar ataxia type-1 is a coordination and speech
disorder in the same disease family.
Biologists knew that mutant forms of the culprit proteins
huntingtin and ataxin-1 accumulate in affected nerve cells.
Truant and his team found that disease-causing versions of
ataxin-1 cannot carry essential RNA molecules out of the
nucleus.
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Abnormal trafficking could have dramatic
repercussions for different types of cell
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Harry Orr
University of Minnesota
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Diseased ataxin-1 moves up to ten times slower than normal,
they saw, by filming living cells. Orr, meanwhile, showed that
one type of RNA accumulates when ataxin-1 is defective.
Huntingtin too, has a section that shuttles other proteins out
of the nucleus, claims Truant.
Other laboratories have recently found that proteins
implicated in Fragile X syndrome and X-linked mental retardation
cannot exit the nucleus or process RNA.
Abnormal trafficking might starve the cell of the correct
RNAs to make proteins. "It could have dramatic repercussions for
different types of cell," says Orr. |
