An overabundance of a protein called STtriatal-Enriched tyrosine Phosphatase (STEP) is linked to the memory decline found in Alzheimer’s patients.
In a recent study carried out by Yale School of Medicine, mice engineered to have Alzheimer’s disease experienced great improvements in learning and memory when these STEP levels were lowered.
Previous research has proven that elevated STEP levels are caused by the harmful peptide beta amyloid that hinders an organelle normally programmed to get rid of these proteins.
“When that organelle is inhibited, proteins, including STEP won’t be degraded and will accumulate,” said Paul Lombroso, M.D., senior author of the study and professor in the Yale Child Study Center.
Furthermore, glutamate receptors found on the surface of neurons play a major role in learning and memory, Lombroso added. He and his team, which included Nobel laureate Paul Greengard of Rockefeller University, found that the high levels of STEP were actually eliminating these glutamate receptors and so preventing short-term memories from becoming long-term memories.
For the study, the scientists observed mice engineered to have Alzheimer’s; although all the mice had the disease, some were engineered to have only the Alzheimer’s mutation without the STEP protein. The researchers wanted to test the idea that lowering STEP levels could reverse mental deficit in Alzheimer’s disease.
The two types of mice (Alzheimer’s with STEP and Alzheimer’s without STEP) were compared in a series of cognitive tests which included a water maze. Mice without the STEP protein were successful at the maze after a 10-day training period; however, the Alzheimer’s mice with the STEP protein were not.
“This tells us that reducing STEP levels is sufficient to reverse the cognitive defect in these mice,” said Lombroso.
In addition to Alzheimer’s, other disorders characterized by cognitive deficits are also associated with elevated levels of STEP in the brain, including schizophrenia and Fragile X. In the same way, higher levels of STEP proteins eliminate glutamate receptors from synapses, adding to the cognitive problems associated with these diseases.
Lombroso believes that these findings provide a basis for drug discovery and for developing treatments that could inhibit STEP proteins and improve the outlook for Alzheimer’s disease patients.
“These new findings need to be replicated, but if genetically reducing STEP levels is improving cognition, we could perhaps discover a drug designed to reduce STEP activity,” said Lombroso. “Our current work is focused on looking for STEP inhibitors.”
The study can be found in the October 18 issue of Proceedings of the National Academy of Sciences and was funded by the American Health Assistance Foundation.
Source: Yale University