American scientists have reported success in preventing the accumulation of toxic proteins associated with Alzheimer’s disease, and the pathology they cause, in animal models, through inhibiting a specific enzyme.
This research, published in the Journal Neuron, took a three-pronged approach to halting the accumulation of toxic proteins in the brain before symptoms of Alzheimer’s disease are evident. By ‘three-pronged’, the scientists tested their theory on human cells grown in a laboratory, fruit flies, and then mice. They found in all their studies they could prevent the accumulation and the subsequent development of brain pathology in their experimental models by inhibiting an enzyme called Nuak1.
However, it wasn’t easy to get to that point and the scientists developed a strategy to screen for genes that decrease the levels of tau.
“We inhibited about 600 kinases one by one and found one, called Nuak1, whose inhibition resulted in reduced levels of tau,” said Dr Huda Zoghbi, who was involved in trial.
The scientists then tried to inhibit Nuak1 in a mouse model of Alzheimer’s disease and hoped that they’d see a similar reduction in Tau, and they did, and also noted improved behaviour and prevention of brain degeneration.
“Confirming in three independent systems – human cells, the fruit fly and the mouse – Nuak1 inhibition results in reduced levels of tau and prevents brain abnormalities induced by tau accumulation, [and] has convinced us that Nuak1 is a reliable potential target for drugs to prevent diseases such as Alzheimer’s,” said Dr Zoghbi.
The next step is for the scientists to develop drugs that will inhibit Nuak1 in hope that one day would be able to lower tau levels with low toxicity in individuals at risk for dementia due to tau accumulation.