Promising Treatment for Parkinson's Disease Prevents Mitochondria-JNK Interaction

These enzymes also play a role in T-cell differentiation and the cellular apoptosis pathway.

To study the role of JNK in Parkinson's disease, investigators at the Scripps Research Institute (Jupiter, FL, USA) induced the disease by administering 6-OHDA (6-hydroxydopamine) either to nerve cell cultures or to a group of laboratory animals.
6-OHDA is a synthetic neurotoxic organic compound used by researchers to destroy selectively dopaminergic and noradrenergic neurons in the brain. It is thought to enter the neurons via the dopamine and noradrenaline (norepinephrine) reuptake transporters. 6-OHDA is used primarily to induce Parkinson's disease in laboratory animals in order to develop and test new medicines for treating Parkinson's disease in humans. In order to induce this condition in animals, around 70% of the dopaminergic neurons in the substantia nigra of the brain must be destroyed, and this is achieved by generating reactive oxygen species such as superoxide radical.

Results published in the January 11, 2013, issue of the Journal of Biological Chemistry revealed that in vitro 6-OHDA induced JNK translocation to the mitochondria and that inhibition of mitochondrial JNK signaling by Tat-SabKIM1 (a cell permeable peptide isolated from the outer mitochondrial membrane) protected against 6-OHDA-induced oxidative stress, mitochondrial dysfunction, and neurotoxicity. Administration of Tat-SabKIM1 via an intracerebral injection into the mid forebrain bundle of the 6-OHDA-treated group of animals doubled the number of tyrosine hydroxylase immunoreactive (TH+) neurons as compared to animals treated only with 6-OHDA into the nigrostriatal pathway.

Overall, these data suggest that 6-OHDA induced JNK translocation to the mitochondria and that blocking this translocation reduced oxidative stress, mitochondrial dysfunction, and neurotoxicity both in vitro and in vivo. Therefore, inhibitors that block JNKs association with the mitochondria may be useful neuroprotective agents for the treatment of Parkinson's disease.

“This may be a novel way to prevent neuron degeneration,” said senior author Dr. Philip LoGrasso, professor of molecular therapeutics at the Scripps Research Institute. “Now we can try to make compounds that block that translocation and see if they are therapeutically viable.”

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