Dynamin linked to Alzheimer's and bipolar disorder

Dynamin is well known for its role in controlling endocytosis, particularly in synaptic vesicles in nerve cells and for its pivotal role in the brain.

Now a new discovery from researchers in Australia and Scotland has linked the activity of dynamin with another key protein, glycogen synthase kinase 3 (GSK3), an enzyme that plays many roles in cell biology.

The researchers found that GSK3 interacts with dynamin and influences the rate of nerve cell communication, with the protein suppressing brain activity by reducing synaptic transmission.

This raises the possibility that drugs could be developed to block the effect of GSK3, increasing chemical messaging between brain cells.

This could help to protect memory in people with Alzheimer’s disease and slow the progression of their illness.

Conversely, drugs could also be developed to boost the effect of the GSK3, slowing brain activity in epilepsy patients and reducing the effects of their seizures.

GSK3 has already been implicated in these disorders, as well as bipolar disorder, and it has been blocked via treatment with lithium, although the mechanism underpinning this treatment was unknown until now.

Professor Phil Robinson, of Sydney's Children's Medical Research Institute, who is a co-author on the paper, says this is a big step towards developing treatments for epilepsy and Alzheimer's.

“We haven’t found a treatment or a cure,” said Robinson. “But we have found how one of the most important targets for the treatment of these conditions works, which opens up the possibility of designing much more effective treatments.”

“I’ve suspected for a long time that dynamin plays a key role in mood disorders, but this research has provided the first really clear evidence.

"We’ve already begun an extensive drug development program using dynamin inhibitors for treatment of epilepsy, so a lot of the information we get from those studies can hopefully be transferred to studies into targeting dynamin for the treatment of Alzheimer's and bipolar disorder.”

Dr Mike Cousin, of the University of Edinburgh, who led the research, said that understanding the role of GSK3 is a breakthrough in being able to treat brain disorders.

“Until now, we understood that this enzyme was important brain cell function, but we did not fully appreciate why. This study shows that GSK3 plays a crucial part in controlling brain function during peak activity. The development of drugs to act on the enzyme could make a real difference to the lives of people with brain disorders.”

The research was conducted in partnership with the University of Dundee in Scotland, the Children’s Medical Research Institute and the Garvan Institute for Medical Research in Sydney.

It was funded by the Wellcome Trust, Epilepsy Research UK and the Australian National Health and Medical Research Council. It was also partly funded by Jeans for Genes, a major fundraiser of CMRI.

The paper was published in Nature Neuroscience, on 6 June, DOI: 10.1038/nn.2571.