Neurodegenerative diseases: another target
A new target for preventing neuronal death in Parkinson's disease
LifeSciencesToday based on TSRI materials:
Scripps Florida Scientists Uncover Potential Drug Target to Block Cell Death in Parkinson’s diseaseOxidative stress is one of the main causes of the development of a number of diseases – from cancer and heart failure to Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease.
Scientists at The Scripps Research Institute (TSRI), Florida, have found that blocking the interaction of one of the most important enzymes can resist the destruction of neurons associated with neurodegenerative diseases and become a new potential target for drug development.
An article on the discovery (Blocking c-jun-N-terminal Kinase (JNK) Translocation to the Mitochondria Prevents 6-hydroxydopamine-induced Toxicity in vitro and in vivo) is published in The Journal of Biological Chemistry.
Under stress conditions, for example, under the influence of ultraviolet radiation, the amount of reactive oxygen species in the cell can significantly increase, which can cause serious damage to it. However, relatively little is known about the role of a number of stress-related enzymes in this process.
A group of researchers led by TSRI Professor Philip LoGrasso focused their attention on an enzyme known as c-jun-N-terminal kinase (c-jun-N-terminal kinase, JNK). Under stress, JNK migrates to mitochondria, cellular organelles that generate chemical energy and are involved in cell growth and death. This migration, combined with JNK activation, is associated with a number of serious health problems, including mitochondrial dysfunction, which has long been known for its contribution to the death of neurons in Parkinson's disease.
Experiments by scientists from the Scripps Institute have shown for the first time that the interaction of JNK with a protein known as Sab (SH3BP5) is responsible for the translocation of JNK into the mitochondria of neurons. In addition, the scientists found that blocking mitochondrial signaling of JNK by inhibiting the interaction of JNK with Sab can prevent damage to neurons both in cell culture and in vivo.
By acting on JNK with the peptide inhibitor Tat-SabKIM1 – a derivative of the outer mitochondrial membrane protein – scientists managed to achieve twice as effective protection of neurons in substantia nigra pars compacta – a brain region that is destroyed in Parkinson's disease.
Importantly, this inhibition does not adversely affect signaling pathways in other cells, which could potentially mean fewer side effects in any of the future drugs.
"This could be a new way to prevent neuron degeneration," says Professor Lo–Grasso. "Now we can try to synthesize compounds that block this translocation and find out if it is possible to create drugs based on them."
Portal "Eternal youth" http://vechnayamolodost.ru14.01.2013