News Feature | August 8, 2014

Scientists Stop Alzheimer's In Mice With STEP Inhibitor

By Estel Grace Masangkay

Mouse test

Researchers from the Yale School of Medicine reported that they have reversed the debilitating effects of Alzheimer’s disease on learning and memory in mice using a new STEP inhibitor compound.

An initial study in PLOS Biology pinpointed a protein implicated in learning and memory dysfunction in patients with Alzheimer’s. High levels of the STriatal-Enriched protein tyrosine Phosphatase (STEP) protein were observed and were overactive in the brains of patients, perhaps because it is not degraded quickly enough. While STEP plays a part in helping a person re-learn something in a new way, overactivity of the protein may disrupt post-synaptic events critical for both learning and memory. High levels of STEP may also keep synapses from strengthening, an activity required to convert short-term memories into long-term ones.

Yale School of Medicine psychiatry professor Paul Lombroso and other scientists examined around 150,000 of molecules and compounds that could inhibit STEP in the brain. Eight of these were found promising. The team then used mice to see if inhibition of STEP would reverse some AD-related cognitive damage. The molecular compound TC-2153 was confirmed to be a potent STEP inhibitor.

In their study also published at PLOS Biology, the scientists reported that TC-2153 improved cognitive function in a number of transgenic mice without change in beta amyloid and phospo-tau levels.

“In summary, we have discovered that the pentathiepin TC-2153 potently inhibits STEP activity… It is important to determine whether TC-2153 is effective in other animal models of neuropsychiatric diseases in which STEP activity is elevated and these studies have begun,” the authors stated.

Commenting on the study, Christianne Kovel, of the state chapter of the Alzheimer's Association, said, “It is an exciting and busy time in Alzheimer's disease research with hundreds of potential therapies being tested at various stages of the research process, and many more being developed.”