Researchers at The University of Texas Health Science Center have now identified a link between the tyrosine kinase, c-Abl, and impaired parkin function. The scientists found that c-Abl was activated in cultured neuronal cells and the striatum of adult mice when subjected to oxidative and neuronal stress. They also identified parkin as a specific substrate for c-Abl and that the tyrosine-phosphorylated parkin lost its ubiquitin ligase activity.
The c-Abl inhibitor, imatinib (STI-571) was able to block the phosphorylation of parkin in vitro and in vivo, restoring ligase activity. Since there are several c-Abl inhibitors approved for the treatment of chronic myelogenous leukemia, tools are available to further explore the neuroprotective potential of c-Abl inhibition in sporadic PD.
The study is published in the Journal of Neuroscience.