Scientists uncover potential drug target to block cell death in Parkinson's disease
January 10, 2013 in Parkinson's & Movement disorders
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."
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/conten… 354.full.pdf
Journal reference:
Journal of Biological Chemistry
Provided by
Scripps Research Institute
-
Scientists find way to block stress-related cell death
Jun 02, 2011 |
not rated yet |
0
-
Key protein interactions involved in neurodegenerative disease revealed
Nov 08, 2012 |
not rated yet |
0
-
Scientists identify key protein linked to acute liver failure
Sep 07, 2011 |
not rated yet |
0
-
New role for the JNK protein
Jul 14, 2010 |
not rated yet |
0
-
Stress Impairs Stem Cell Function in Aging Tissues
Feb 02, 2009 |
not rated yet |
0
-
Motion perception revisited: High Phi effect challenges established motion perception assumptions
Apr 23, 2013 |
3 / 5 (2) |
2
-
Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update)
Apr 02, 2013 |
4.5 / 5 (11) |
5
-
The visual system as economist: Neural resource allocation in visual adaptation
Mar 30, 2013 |
5 / 5 (2) |
9
-
Separate lives: Neuronal and organismal lifespans decoupled
Mar 27, 2013 |
4.9 / 5 (8) |
0
-
Sizing things up: The evolutionary neurobiology of scale invariance
Feb 28, 2013 |
4.8 / 5 (10) |
14
-
Angular Frequency of AC voltage
2 hours ago
-
Modeling Rigid Body - Unsure about Euler angles and angular velocity
2 hours ago
-
Function for a bullet's path
3 hours ago
-
Elementary questions relating to Newton's laws of motion
5 hours ago
-
Magnetic Energy of Solenoid With/Without Core
5 hours ago
-
Static Equilibrium and D'Alembert's Principle
5 hours ago
- More from Physics Forums - Classical Physics
More news stories
Diabetes drug tested in Parkinson's disease patients
Parkinson's disease (PD) is a degenerative neurological disorder marked by a progressive loss of motor control. Despite intensive research, there are currently no approved therapies that have been demonstrated to alter the ...
Parkinson's & Movement disorders
11 hours ago |
not rated yet |
0
Faulty energy production in brain cells leads to disorders ranging from Parkinson's to intellectual disability
Neuroscientist Patrik Verstreken of VIB (Flanders Institute for Biotechnology) and KU Leuven has shown for the first time that dysfunctional mitochondria in brain cells can lead to learning disabilities. The link between ...
Parkinson's & Movement disorders
May 17, 2013 |
4 / 5 (2) |
0
Unleashing the watchdog protein
McGill University researchers have unlocked a new door to developing drugs to slow the progression of Parkinson's disease. Collaborating teams led by Dr. Edward A. Fon at the Montreal Neurological Institute and Hospital -The ...
Parkinson's & Movement disorders
May 09, 2013 |
5 / 5 (1) |
0
|
Could eating peppers prevent Parkinson's? Dietary nicotine may hold protective key
New research reveals that Solanaceae—a flowering plant family with some species producing foods that are edible sources of nicotine—may provide a protective effect against Parkinson's disease. The study appearing today ...
Parkinson's & Movement disorders
May 09, 2013 |
not rated yet |
0
Study shows how Parkinson's disease protein acts like a virus
A protein known to be a key player in the development of Parkinson's disease is able to enter and harm cells in the same way that viruses do, according to a Loyola University Chicago Stritch School of Medicine study.
Parkinson's & Movement disorders
Apr 25, 2013 |
5 / 5 (5) |
0
|
The compound in the Mediterranean diet that makes cancer cells 'mortal'
New research suggests that a compound abundant in the Mediterranean diet takes away cancer cells' "superpower" to escape death. By altering a very specific step in gene regulation, this compound essentially re-educates cancer ...
Do salamanders hold the solution to regeneration?
Salamanders' immune systems are key to their remarkable ability to regrow limbs, and could also underpin their ability to regenerate spinal cords, brain tissue and even parts of their hearts, scientists have ...
Scientists identify molecular trigger for Alzheimer's disease
Researchers have pinpointed a catalytic trigger for the onset of Alzheimer's disease – when the fundamental structure of a protein molecule changes to cause a chain reaction that leads to the death of neurons ...
Practice makes perfect? Not so much
Turns out, that old "practice makes perfect" adage may be overblown. New research led by Michigan State University's Zach Hambrick finds that a copious amount of practice is not enough to explain why people ...
Older prostate cancer patients should think twice before undergoing treatment
Older prostate cancer patients with other underlying health conditions should think twice before committing to surgery or radiation therapy for their cancer, according to a multicenter study led by researchers in the UCLA ...
New test better detects elephantiasis worm infection
A new diagnostic test for a worm infection that can lead to severe enlargement and deformities of the legs and genitals is far more sensitive than the currently used test, according to results of a field ...