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York Biomedical Research Institute
HomeYork Biomedical Research InstituteBrain healthMicrotubule disorganisation emerges as a new driver of neurodegeneration

Microtubule disorganisation emerges as a new driver of neurodegeneration

The Hahn lab studies how signalling pathways and the cytoskeleton shape neuronal development, function and maintenance.

Combining live-cell imaging, Drosophila and mammalian models with tools such as optogenetics, biosensors and peptide inhibitors, we uncover disease mechanisms ranging from Alzheimer's disease to Neurofibromatosis type 1 and connect molecular events to neuronal function and behaviour.

In a recent study we show that the enzyme GSK-3β, which has long been linked to neurodegeneration, must be kept within a very narrow range of activity to maintain orderly bundles of microtubules in neurons. Neurons depend on neatly organised, parallel bundles of tiny tubes called microtubules to maintain their shape and deliver vital cellular supplies. 

The authors of this study discovered that GSK-3β operates like a precise master dial regulating two key helper proteins Tau and Shot. When GSK-3β activity strays even slightly from its optimal range (whether becoming overactive or underactive) these d structural bundles unravel into tangled curls, forming damaging swellings along the cell. 

Crucially, these insights explain why clinical trials aiming to treat Alzheimer’s disease by completely blocking GSK-3β have repeatedly failed: because disabling the enzyme entirely causes just as much structural decay and functional loss as having too much of it, showing that future treatments must carefully fine-tune GSK-3β rather than turn it off.

 Publication

Lead researcher