|
|
December 16, 2002
STUDY SHOWS MITOCHONDRIA LIKELY
GO AWRY IN ALS
A scientist new to The Packard Center for ALS Research has shown that
key reactions in mitochondria, the small bodies within cells that supply
energy to cells, are disrupted just before cells begin to die from the
disease. Work by Giovanni Manfredi, M.D., Ph.D., and his research team
support the idea that injury to mitochondria is a step leading to the
actual death of motor neurons--the main site of injury in ALS.
Manfredi's work was carried out in mouse ALS models that carry a mutated
human gene coding for a protein called superoxide dismutase 1 (SOD1).
People with mutant SOD1 genes develop a specific inherited form of the
disease.
Studies by others have shown that ALS patients--those with either the
inherited or the more common "spontaneous" form---often have mitochondria
that are swollen and/or misshapen. Mitochondria in mouse models are also
clearly in trouble.
The work by the Manfredi team, published recently in the Journal of Biological
Chemistry, showed that, in addition to having an altered appearance, mitochondria
were also impaired in function, in their chemical reactions that produce
energy. This was especially obvious in the spinal cord, which happens
to be the body site most affected in ALS. The study is the first to show
mutated SOD1 leads to a loss of the normal activity of mitochondria in
standard mouse models of ALS.
The changes in the tiny organelles didn't appear before the model mice
were 13 weeks old, about six weeks before their death. This suggests that
mitochondrial changes may not be the event that triggers ALS, but may
be closely related to the actual death of cells.
Confirming results of other Center scientists, Manfredi also found that
both mutant and normal SOD1 appear to collect in small compartments within
mitochondria. But only the mutant form seems to be linked with problems.
"We don't understand how it causes dysfunction," Manfredi says, "but we're
testing the possibilities."
One idea is that mutant SOD1 is somehow "warped" and can't function properly.
Normal SOD1 is an enzyme that destroys a highly reactive molecule called
superoxide, a destructive molecule that's a byproduct of energy-making
in mitochondria. It's possible, the researchers say, that a shortage of
normal SOD1 leaves superoxide free to damage mitochondria. Manfredi's
team, in fact, found evidence of that sort of damage.
Another idea is that mutant SOD1 accumulates in mitochondria,"gumming
up" normal processes. The team, as have other Center researchers, also
found evidence of accumulated mutant SOD1 within and near the outer membrane
of mitochondria.
Whatever the cause of mitochondrial distress, Manfredi says; understanding
its source and the relation to motor neuron damage could eventually provide
targets for needed therapy.
The research team is located at the Weill Medical College of Cornell University.
more Recent News
|
|
|
|
| Recent news from the Robert Packard Center
for ALS Research: |
| In ALS, It’s Not the Number of Ailing Astrocytes That Counts - June 12, 2008 |
| Leaky Blood Vessels Add To ALS Damage, Could Offer New Repair Site - June 10, 2008 |
| William H. Adams Foundation Pumps New Energy, Funds into Search for ALS Cure - May 6, 2008 |
| Tell-Tale Protein Clumping in ALS is Less Complex Than Expected - April 10, 2008 |
ALS Mouse Study Highlights Astrocytes' Strong Potential as Therapy Target - February 7, 2008 |
| Exciting New Human ALS Trial: Lithium and Riluzole - February 7, 2008 |
| ALS Treatment: A Matter of Cleaning House? - December 19, 2007 |
New Study Brings What Goes Wrong in Inherited ALS into Focus - September 18, 2007 |
| New ALS Protein Could Be a Keystone - August 9, 2007 |
| Muscles More Than Passive Victims in ALS, Study Suggests - June 29, 2007 |
| Saer and O’Neill Named Packard Center Board Co-Chairs - June 28, 2007 |
Self-Attack? Self-Repair? First Real Look at Gene Activity in ALS Models Sparks Thirst for Answers - May 3, 2007 |
| Model of Accelerated Familial ALS Sheds Light on Disease Process - April 6, 2007 |
| Early News From First Large Search for Sporadic ALS Genes - February 20, 2007 |
| Human Stem Cell Transplants Mature Into Neurons and Make Contacts in Rat Spinal Cord - February 14, 2007 |
|
