Enzyme Nuak1 is a reliable potential target which can be used in drugs to prevent diseases such as Alzheimer's, finds a research.
Enzyme Nuak1 helps to prevent accumulation of toxic molecules in the brain.
The study, published in Cell Press journal Neuron, took a three-pronged approach to help subdue early events that occur in the brain long before symptoms of Alzheimer's disease are evident.
The scientists were able to prevent those early events and the subsequent development of brain pathology in experimental animal models in the lab.
"Common diseases like Parkinson's, Alzheimer's and dementia are caused in part by abnormal accumulation of certain proteins in the brain," said Huda Zoghbi, Professor at the Baylor College of Medicine, US.
Some proteins become toxic when they accumulate; they make the brain vulnerable to degeneration. Tau is one of those proteins involved in Alzheimer's disease and dementia, suggested the study.
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"Scientists in the field have been focusing mostly on the final stages of Alzheimer's disease. Here we tried to find clues about what is happening at the very early stages of the illness, before clinical irreversible symptoms appear," said Cristian Lasagna-Reeves, researcher at the Baylor College of Medicine.
The scientists reasoned that if they could find ways to prevent or reduce Tau accumulation in the brain, they would uncover new possibilities for developing drug treatments for these diseases.
To find which enzymes affect Tau accumulation, the scientists systematically inhibited enzymes called Kinases.
"We inhibited about 600 Kinases one by one and found one, called Nuak1, whose inhibition resulted in reduced levels of Tau," Zoghbi added.
The scientists screened the enzymes in two different systems, cultured human cells and the laboratory fruit fly. Screening in the fruit fly allowed the scientists to assess the effects of inhibiting the enzymes in a functional nervous system in a living organism.
"We found one enzyme, Nuak1, whose inhibition consistently resulted in lower levels of Tau in both human cells and fruit flies. Then we took this result to a mouse model of Alzheimer's disease and hoped that the results would hold, and they did. Inhibiting Nuak1 improved the behaviour of the mice and prevented brain degeneration," Zoghbi added.
Confirming in three independent systems - human cells, the fruit fly and the mouse - that Nuak1 inhibition results in reduced levels of Tau and prevents brain abnormalities induced by toxic accumulation.
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