10:54pm Thursday 09 April 2020

Has a possible new lead been found in the fight against neurodegenerative diseases?

Patrik Verstreken (VIB/KU Leuven): “These unexpected results offer us a new line of approach for research into communication between brain cells. We feel that in time it should be possible to help patients with mutations in the TBC1D24 gene, by partially inhibiting transport to the lysosomes (compartments in the cell that digest various molecules).”

A good model for the study of neurodegenerative diseases
We know that mutations in the TBC1D24 gene cause a brain disorder that brings with it conditions including extensive neurodegeneration, epilepsy, mental retardation and hearing problems. Patrik Verstreken and his colleagues have developed fruit flies with mutations in the Skywalker gene, the fruit fly version of TBC1D24. These fruit flies display similar symptoms to patients with brain disorders.

Patrik Verstreken explains: “These fruit flies are not only a suitable model for investigating what goes wrong in the brain, but also for exploring how this can be tackled. For instance we are attempting to reduce or eliminate the symptoms in the fruit flies with mutations in Skywalker by introducing further changes to their DNA. If successful, it means that we have new starting points for our research into neurodegeneration.”

Need for “contaminated, defective” proteins
Brain cells communicate with one another at a synapse. Ana Clara Fernandes, Valerie Uytterhoeven and their colleagues, led by Patrik Verstreken, were screening for genes with a potential impact on communication between brain cells. In the process they came across HOPS complex genes. The HOPS complex ensures that contaminated, defective proteins at the synapse (where brain cells communicate with one another) are transported to the lysosome, the compartment of the cell responsible for breaking down the proteins.

When the VIB researchers cut out half of the HOPS complex genes in their fruit fly model for neurodegeneration, the flies were found to be no longer ill. Initially this seems rather strange, because a less active HOPS complex means that the transport of defective proteins to the degradation site is not working as well as it should. This research has shown, however, that defective proteins also play a role at the synapse. These surprising results offer a new line of approach for research into brain disorders.

As this research may raise questions, we want to ask you to list the e-mail address that the VIB has made available for questions in your report or article. Everyone can contact us with questions about this research and other medical research: [email protected].

Reduced synaptic vesicle protein degradation at lysosomes curbs TBC1D24/sky-induced neurodegeneration Fernandes, Uytterhoeven et al., The Journal of Cell Biology 2014

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