C-PALSY Archives

Cerebral Palsy List

C-PALSY@LISTSERV.ICORS.ORG

Options: Use Forum View

Use Monospaced Font
Show Text Part by Default
Show All Mail Headers

Message: [<< First] [< Prev] [Next >] [Last >>]
Topic: [<< First] [< Prev] [Next >] [Last >>]
Author: [<< First] [< Prev] [Next >] [Last >>]

Print Reply
Subject:
From:
Meir Weiss <[log in to unmask]>
Reply To:
Cerebral Palsy List <[log in to unmask]>
Date:
Fri, 20 Oct 2006 15:17:25 -0400
Content-Type:
text/plain
Parts/Attachments:
text/plain (159 lines)
http://www.dana-farber.org/abo/news/press/2006/scientists-identify-switch-for-br
ains-natural-anti-oxidant-defense.html


/ Home / About Dana-Farber / News & Publications / Press Releases / 
Main Menu Skip to content Mission and Values
 
Facts & Figures
 
History
 
News & Publications
 Press Releases
 
Press Release Archive
 
New Building Updates
 
For Journalists
 
Facts & Figures
 
Publications
 
Links to Journals
 
Dana-Farber in the News
 
Dana-Farber Physicians & Researchers
 
Medical Education & Training
 
Community Outreach
 
Collaborations
 
DFCI Directories
 
Working at Dana-Farber
 
DFCI Awards
 
Leadership Profiles
 
Why Dana-Farber?
 
Satellite Clinics
 

 Press Releases 

October 20, 2006
Scientists identify switch for brain's natural anti-oxidant defense
Finding suggests potential strategy for treating Alzheimer's, Parkinson's, other
brain diseases
 
Bruce Spiegelman, PhD
Scientists at Dana-Farber Cancer Institute report they have found how the brain
turns on a system designed to protect its nerve cells from toxic "free
radicals," a waste product of cell metabolism that has been implicated in some
degenerative brain diseases, heart attacks, strokes, cancer, and aging. 

Potentially, the researchers say, it may be possible to use drugs to strengthen
the anti-oxidant system in the brain as a treatment for presently incurable
diseases like Parkinson's, Huntington's, and Alzheimer's and possibly other
maladies. 

Dana-Farber's Bruce Spiegelman, PhD, and colleagues, using a mouse model,
discovered that a regulatory protein, PGC-1a, switches on the anti-oxidant
system when free radicals, or reactive oxygen species, begin to accumulate. It's
believed that some brain diseases involve a failure of the protective system,
and the authors report that turning on PGC-1a to high levels in cultured cells
protected them against nerve toxins. The findings will be reported in the Oct.
20 issue of the journal Cell. 

"This could have broad implications for the many diseases in which reactive
oxygen species are implicated," said Spiegelman. Anti-oxidant supplements have
been used with some success in patients with neurodegenerative diseases, but
Spiegelman noted that the process sparked by PGC-1a "is how nature does it." 

Researchers currently are screening drugs in search of compounds that could spur
PGC-1a expression in brain cells, as well as exploring whether any harmful side
effects might result. PGC-1a is a transcriptional co-activator discovered in
Spiegelman's Dana-Farber laboratory in 1998. It has subsequently been found to
play a master regulatory role in metabolic processes and muscle function, as
well as being a culprit in diabetes. 

The report establishes for the first time that PGC-1a both drives the
mitochondria to make energy and triggers the cleanup of toxic free radicals that
accumulate in the cell as byproducts. As excess free radicals build up, their
toxicity places the cell under "oxidative stress," which prompts the cell to
produce more PGC-1a, which in turn spurs the anti-oxidant defenses into action. 

"With this mechanism, the body can speed up mitochondrial formation and at the
same time suppress the creation of reactive oxygen species, which are known to
be terribly damaging to the cell," explains Spiegelman, who is also a professor
of cell biology at Harvard Medical School. In this respect, the cell could be
compared to a self-cleaning oven - but one that becomes less efficient with age
and in certain diseases. 

Therefore, the new finding of a specific regulator of the body's own
anti-oxidant system could lead to more-effective treatments for a number of
diseases, and might even retard some of the effects of aging, the researchers
say. 

In previous experiments, Spiegelman and others had bred mice that lacked the
PCG-1a gene. As would be expected, the absence of PCG-1a caused the mice to have
abnormalities in their metabolism - they had less exercise capacity and were
extremely sensitive to cold. But what the scientists hadn't predicted was that
the mice had neurodegenerative lesions in their brains and behaved abnormally:
This was a clue that without PGC-1a, the cells' "self-cleaning" mechanism wasn't
activated properly, leaving the mice more vulnerable to brain damage from
renegade free radicals. 

In the current research, Spiegelman and his colleagues exposed normal mice and
rodents lacking PGC-1a to a nerve toxin that accelerates the production of free
radicals. Mice without PGC-1a suffered more brain damage because they couldn't
turn on their anti-oxidant defenses. 

Finally, to investigate whether increasing PGC-1a activity in the brain would
protect against oxidative stress, the scientists caused mouse brain cells and
human brain cells in the laboratory to make 40 times as much PCG-1a as normal.
They exposed the cells to increasing amounts of paraquat or hydrogen peroxide,
chemicals that cause oxidative stress and cell damage. The result: many more
brain cells survived the assault than did cells without the extra PGC-1a
activity to augment their defenses. 

Because PGC-1a has now been shown both to rev up energy production in the
mitochondria and to suppress the resulting free radicals, "this is an almost
ideal protein to control or limit the damage seen in neurodegenerative diseases
that have been associated with defective mitochondrial function," the authors
wrote. As a result, finding drugs that increase PGC-1a in the brain "could
represent a new mode of therapy for a set of diseases that are both common and
have only marginal therapies at this moment." 

Lead authors of the report are Julie St-Pierre, PhD, and Stavit Drori, PhD,
formerly of Dana-Farber and Harvard Medical School. The paper's co-authors are
based at Dana-Farber, Beth Israel Deaconess Medical Center, and Harvard Medical
School. 

The research was funded in part by the National Institutes of Health.

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching
affiliate of the Harvard Medical School and is among the leading cancer research
and care centers in the United States. It is a founding member of the
Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer
center by the National Cancer Institute.

Media Contacts
Richard Saltus
Bill Schaller
(617) 632-4090

-----------------------

To change your mail settings or leave the C-PALSY list, go here:

http://listserv.icors.org/SCRIPTS/WA-ICORS.EXE?SUBED1=c-palsy

ATOM RSS1 RSS2