ironjustice
2013-01-15 04:25:58 UTC
Blocking interaction of JNK enzyme may counteract neuron destruction
Published on January 11, 2013 at 4:57 AM
Oxidative stress is a primary villain in a host of diseases that range
from cancer and heart failure to Alzheimer's disease, Amyotrophic
Lateral Sclerosis and Parkinson's disease. Now, scientists from the
Florida campus of The Scripps Research Institute (TSRI) have found
that blocking the interaction of a critical enzyme may counteract the
destruction of neurons associated with these neurodegenerative
diseases, suggesting a potential new target for drug development.
These findings appear in the January 11, 2013 edition of The Journal
of Biological Chemistry.
During periods of cellular stress, such as exposure to UV radiation,
the number of highly reactive oxygen-containing molecules can increase
in cells, resulting in serious damage. However, relatively little is
known about the role played in this process by a number of stress-
related enzymes.
In the new study, the TSRI team led by Professor Philip LoGrasso
focused on an enzyme known as c-jun-N-terminal kinase (JNK). Under
stress, JNK migrates to the mitochondria, the part of the cell that
generates chemical energy and is involved in cell growth and death.
That migration, coupled with JNK activation, is associated with a
number of serious health issues, including mitochondrial dysfunction,
which has long been known to contribute to neuronal death in
Parkinson's disease.
The new study showed for the first time that the interaction of JNK
with a protein known as Sab is responsible for the initial JNK
localization to the mitochondria in neurons. The scientists also found
blocking JNK mitochondrial signaling by inhibiting JNK interaction
with Sab can protect against neuronal damage in both cell culture and
in the brain.
In addition, by treating JNK with a peptide inhibitor derived from a
mitochondrial membrane protein, the team was able to induce a two-fold
level of protection of neurons in the substantia nigra pars compacta,
the brain region devastated by Parkinson's disease.
The study noted that this inhibition leaves all other cell signaling
intact, which could mean potentially fewer side effects in any future
therapies.
"This may be a novel way to prevent neuron degeneration," said
LoGrasso. "Now we can try to make compounds that block that
translocation and see if they're therapeutically viable."
Source: Scripps Research Institute
-------------
"Oxidative Stress and Redox-Active Iron in Alzheimer's Disease"
http://www.ncbi.nlm.nih.gov/pubmed/15105265
"Inhibition of JNK signaling depends on suppressing ROS accumulation
and is achieved through iron sequestration"
http://www.sciencedirect.com/science/article/pii/S0092867404009985
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
Published on January 11, 2013 at 4:57 AM
Oxidative stress is a primary villain in a host of diseases that range
from cancer and heart failure to Alzheimer's disease, Amyotrophic
Lateral Sclerosis and Parkinson's disease. Now, scientists from the
Florida campus of The Scripps Research Institute (TSRI) have found
that blocking the interaction of a critical enzyme may counteract the
destruction of neurons associated with these neurodegenerative
diseases, suggesting a potential new target for drug development.
These findings appear in the January 11, 2013 edition of The Journal
of Biological Chemistry.
During periods of cellular stress, such as exposure to UV radiation,
the number of highly reactive oxygen-containing molecules can increase
in cells, resulting in serious damage. However, relatively little is
known about the role played in this process by a number of stress-
related enzymes.
In the new study, the TSRI team led by Professor Philip LoGrasso
focused on an enzyme known as c-jun-N-terminal kinase (JNK). Under
stress, JNK migrates to the mitochondria, the part of the cell that
generates chemical energy and is involved in cell growth and death.
That migration, coupled with JNK activation, is associated with a
number of serious health issues, including mitochondrial dysfunction,
which has long been known to contribute to neuronal death in
Parkinson's disease.
The new study showed for the first time that the interaction of JNK
with a protein known as Sab is responsible for the initial JNK
localization to the mitochondria in neurons. The scientists also found
blocking JNK mitochondrial signaling by inhibiting JNK interaction
with Sab can protect against neuronal damage in both cell culture and
in the brain.
In addition, by treating JNK with a peptide inhibitor derived from a
mitochondrial membrane protein, the team was able to induce a two-fold
level of protection of neurons in the substantia nigra pars compacta,
the brain region devastated by Parkinson's disease.
The study noted that this inhibition leaves all other cell signaling
intact, which could mean potentially fewer side effects in any future
therapies.
"This may be a novel way to prevent neuron degeneration," said
LoGrasso. "Now we can try to make compounds that block that
translocation and see if they're therapeutically viable."
Source: Scripps Research Institute
-------------
"Oxidative Stress and Redox-Active Iron in Alzheimer's Disease"
http://www.ncbi.nlm.nih.gov/pubmed/15105265
"Inhibition of JNK signaling depends on suppressing ROS accumulation
and is achieved through iron sequestration"
http://www.sciencedirect.com/science/article/pii/S0092867404009985
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk