Researchers at the Baylor College of Medicine, Texas Children's Hospital, and John Hopkins University School of Medicine took a three-pronged approach to help subdue early events that occur in the brain long before symptoms for Alzheimer's disease appear.
Senior author Huda Zoghbi said, "Common diseases like Parkinson's, Alzheimer's, and Dementia, are caused in part by abnormal accumulation of certain proteins in the brain. Some proteins become toxic when they accumulate, they make the brain vulnerable to degeneration. Tau is one of these proteins involved in Alzheimer's disease and dementia." First author Cristian Lasagna-Reeves said, "We tried to find clues about what is happening at the very early stages of the illness, before clinical irreversible symptoms appear, with the intention of preventing our reducing those early events that lead to devastating changes in the brain decades later." She added, "We inhibited about 600 kinases one by one and found one, called Nuak1, whose inhibition resulted in reduced levels of tau."
The involved scientists screened the enzymes in two different systems, cultured human cells and the laboratory fruit fly. Screening the fly allowed them to assess the effects of inhibiting the enzymes in a functional nervous system in a living organism. "Inhibition of Nuak1 consistently resulted in lower levels of tau in both, human cells, and fruit flies. Then we took the result to a mouse model of Alzheimer's disease and hoped that the results would hold, and they did. Inhibiting Nuak1 improve the behaviour of the mice and prevented brain degeneration," Zoghbi said. "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 tau accumulation, has convinced us that Nuak1 is a reliable potential target for drugs to prevent diseases such as Alzheimer's."
