Scientists uncover potential drug target to block cell death in Parkinson's disease

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 .

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."

More information: "Blocking c-jun-N-terminal Kinase (JNK) Translocation to the Mitochondria Prevents 6-hydroxydopamine-induced Toxicity in vitro and in vivo" www.jbc.org/content/early/2012… M112.421354.full.pdf

Related Stories

Scientists find way to block stress-related cell death

Jun 02, 2011

Scientists from the Florida campus of The Scripps Research Institute have uncovered a potentially important new therapeutic target that could prevent stress-related cell death, a characteristic of neurodegenerative diseases ...

New role for the JNK protein

Jul 14, 2010

Put simply, a tumor is the result of out-of-control cell growth. To assure that the cell cycle - the cell's process of duplicating itself to make more cells - goes smoothly, a large network of proteins tells other proteins ...

Stress Impairs Stem Cell Function in Aging Tissues

Feb 02, 2009

(PhysOrg.com) -- Heinrich Jasper, assistant professor of biology at the University of Rochester, has won a $900,000 Senior Fellow Award from the Ellison Medical Foundation for his work showing how stress affects stem cell ...

Recommended for you

Parkinson's disease reverted at a experimental stage

Dec 19, 2014

Mexican scientists demonstrated experimentally, with adult rats, that mobility can be restored in patients with Parkinson's disease, the major degenerative disease of the motor system worldwide. The experiments ...

EU team launches clinical trial of Parkinson's vaccine

Dec 09, 2014

Today the EU-consortium SYMPATH starts recruitment for a Phase I study of a Parkinson's vaccine candidate called AFFITOPE PD03A. This vaccine is one out of a designated pool of promising vaccine candidates based on AFFiRiS' ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.