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| Prion protein can be infectious, spreading from cell to cell in the brain. Here four nerve cells in a mouse illustrate how infectious prion protein moves within cells along neurites — wire-like connections the nerve cells use for communicating with adjacent cells. |
Alzheimer's, Parkinson's and
amyotrophic lateral sclerosis ravage the brain in very different ways. But they
have at least one thing in common, says Corinne Lasmezas,
a neuroscientist and professor at Scripps Research Institute, in Jupiter, Fla.
Each spreads from brain cell to brain cell like an infection.
"So if we could block this
[process], that might prevent the diseases," Lasmezas says.
It's an idea that's being embraced
by a growing number of researchers these days, including Nobel laureate Dr. Stanley
Prusiner, who first recognized in the 1980s the infectious nature of
brain proteins that came to be called prions. But the idea that
mad cow prions could cause disease in people has its origins in an epidemic of
mad cow disease that occurred in Europe and the U.K. some 15 years ago.
Back then, Lasmezas was a young
researcher in France studying how mad cow, formally known as bovine spongiform
encephalopathy, was transmitted. "At that time, nobody knew if this new
disease in cows was actually transmissible to humans," she says.
In 1996, Lasmezas published a study
strongly suggesting that it was. "So that was my first great research
discovery," she says.
In 2005, Lasmezas came to Scripps
Florida, where she continued to study the toxic particles responsible for mad
cow and its human equivalent.
"These aggregated proteins are
not only transmissible from cell to cell in prion diseases, they are also
transmissible cell to cell in Alzheimer's disease, in Parkinson's disease, in
ALS."
- Corinne Lasmezas, neuroscientist,
Scripps Florida
Prions, it turns out, become toxic
to brain cells when folded into an abnormal shape. "This misfolded protein
basically kills the neurons," Lasmezas says.
Neurons, like other cells, depend
on proteins to carry out essential tasks, like defending against germs and
regulating metabolism. But to function correctly, a protein must be folded into
exactly the right shape. If it folds into the wrong shape, it can kill a cell.
As scientists learned more about
prion diseases like mad cow, they began to realize that misfolded proteins had
a role in several human brain diseases. "Little by little," Lasmezas
says, "it became clear that there are a lot of common features between
prion diseases and the other diseases like Alzheimer's, Parkinson's,
amyotrophic lateral sclerosis."
Cows in England suspected of
having mad cow disease in 1996. The illness was traced to particular proteins
that gummed up brain tissue because they didn't fold properly.
In prion diseases like mad cow, the
misfolded proteins spread by somehow causing normal, adjacent proteins to
change shape. So a few years ago, researchers looked to see whether the
abnormal proteins spread from neuron to neuron the same way in other brain
diseases.
The evidence
was clear, Lasmezas says. "These aggregated proteins are not only
transmissible from cell to cell in prion diseases, they are also transmissible
cell to cell in Alzheimer's disease, in Parkinson's disease, in ALS."
"What we found is ... if you
replenish NAD in these neurons, it completely protects them against the injury
caused by misfolded prion proteins."
When these misfolded proteins reach
a critical mass, they appear to start a chain reaction that eventually destroys
the brain. So Lasmezas and many other researchers are looking for ways to slow
or halt that chain reaction.
One approach is to find drugs that
can neutralize misfolded proteins before they spread. Another is to protect
brain cells from the damage usually caused by a misfolded protein. Lasmezas and
her colleague Minghai Zhou are part of a team that describe
a way to do this in the current issue of the journal Brain.
The experiment involved a prion
protein that kills neurons by depleting their supply of a molecule called NAD.
"What we found is that if you
replenish NAD in these neurons, it completely protects them against the injury
caused by misfolded prion protein," Lasmezas says.
That suggests the right drugs could
protect brain cells from the misfolded proteins involved in Alzheimer's and
Parkinson's and ALS, Lasmezas says.
But protecting cells is an approach
designed to slow down brain diseases, not stop them. To stop the problem, she
says, researchers will have to figure out precisely how normal proteins become
corrupted. "We need to understand how they change their shape. What makes
them misfold? What happens to them?"
The research on misfolded proteins
is changing how scientists view diseases like Alzheimer's and Parkinson's, says
Margaret
Sutherland, a program director at the National Institute of
Neurological Disorders and Stroke, which funds Lasmezas' research. "It's
opened up a different mechanism for understanding the pathology behind
neurodegenerative diseases," she says.
But there's still no way of
knowing, she adds, whether this new understanding will lead to new treatments
for these diseases.
http://www.npr.org/blogs/health/2015/03/09/390980364/mad-cow-research-hints-at-ways-to-halt-alzheimers-parkinsons
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