The brain, spinal cord and optic nerves are summarized as the central nervous system. Nerve fibers, the so-called axons, cannot reproduce after injury, so the damage is permanent. "The ability to regenerate nerve cells in the central nervous system can be partially restored by removing the inhibitory protein PTEN," explains Dietmar Fischer. "However, this so-called knockout causes many different reactions in the cells at the same time, which also often leads to cancer." For this reason, direct inhibition of this protein for therapeutic approaches in humans is not appropriate. Also, the originally postulated mechanism based on the renewed ability to regenerate after a PTEN stroke could not be confirmed by further research, so researchers sought alternative explanations.
Only allow positive effects
In their investigations into this still unclear mechanism, Bochum scientists were able to show for the first time that the PTEN knockout strongly inhibited an enzyme called glycogen synthase kinase-3, or GSK3. This enzyme in turn blocks another protein called the collapsin-2 response mediator protein, CRMP2. That is, the PTEN knockout prevents CRMP2 from inhibiting GSK3. "If we directly prevent this second step and thus prevent CRMP2 inhibition, we can also more specifically achieve the effect of promoting regeneration," explains Dietmar Fischer. Activation of CRMP2 itself is not known to be carcinogenic.
Access new medicines
"Although we have demonstrated these effects only in genetically engineered mice and gene therapy approaches, these findings open new opportunities for the development of new approaches to drugs," explains the neuropharmacologist. Further investigations on his chair address these possibilities.
The work was funded by the Deutsche Forschungsgemeinschaft.
Editor: Meike Drießen
Prof. Dietmar Fischer
Department of Cell Physiology
Faculty of Biology and Biotechnology
Ruhr Bochum University
Phone: 0234 32 29602
Marco Leibinger, Alexander Hilla, Anastasis Andreadaki: GSK3-CRMP2 signaling mediates axonal regeneration induced by PTEN knockout, in: Nature Communications Biology, 2019, DOI: 10.1038 / s42003-019-0524-1