Alzheimer’s: targeting a protein to delay the disease

Preventing the accumulation of toxic proteins in the brain would delay the onset of Alzheimer’s disease, suggests a study published in Neuron. A strategy that has proven effective in laboratory guinea pigs.

Alzheimer’s disease and dementias are very slowly evolving neurodegenerative pathologies. Memory loss, disorientation, speech or writing disorders manifest themselves more than a decade after the onset of the disease.
“Until now, scientists have focused on the late stages of Alzheimer’s disease,” explains Dr. Cristian Lasagna-Reeves, one of the study’s authors and researcher at Baylor University (United States). We wanted to understand what was happening at the very onset of the disease, long before the first irreversible clinical signs appeared, with the intention of preventing or reducing events leading to devastating damage years later ”.

This degeneration is caused by two molecules: the amyloid plaques and the Tau protein synthesized by neuronal cells. Their accumulation in the brain promotes the disorganization of neurons and their death. The researchers then speculated that by avoiding the aggregation of Tau proteins, they could prevent the onset of Alzheimer’s.

Prevent and treat

To do this, the researchers targeted an enzyme responsible for the production of the Tau protein called Nuak1. By blocking this molecule, they observed a decrease in the level of Tau protein in human brain cells and the Drosophila fly. A reduction also visible in the living insect.

In addition, they were able to confirm the role of this enzyme in mice. When Nuak1 is inhibited, the concentration of Tau proteins drops which prevents it from accumulating in the animal’s brain and causing degeneration.
Even more interesting, in mice suffering from Alzheimer’s disease, blocking the Nuak1 enzyme made it possible to improve their behavior and prevent the appearance of new lesions.

For researchers, these results indicate that Nuak1 is a therapeutic target for slowing or treating Alzheimer’s disease or other dementias. “Just like patients who take cholesterol medications to prevent cardiovascular disease, we can imagine that in the future those at risk for Alzheimer’s disease could take medications that keep the Tau protein low. », Hopes Dr Cristian Lasagna-Reeves.